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Hepatocellular carcinoma (HCC), one of the malignancies with a wide expression of stress ligands recognized by Vδ1γδ T cells, has received much attention in adoptive immunotherapy of γδ T cells. In this study, we aimed to identify the potential anti-tumor Vδ1γδ T subpopulations in HCC. Healthy donors (HDs) and HCC patients were recruited from the Affiliated Cancer Hospital of Zhengzhou University. Blood and tumor tissue samples were obtained respectively. Bioinformatics methods were used to analyze total γδ T cells and subsets infiltration, overall survival of HCC patients with high and low infiltration level of Vδ1γδ T cells, and IFNG , granzyme A, granzyme B and perforin expression in TRDV1 high/low CD69 high/low groups. CD69 expression and Vδ1γδT cells infiltration in HCC were detected by immunofluorescence. Phenotypic analysis of Vδ1γδ T cells in blood and tumor tissue samples were performed by flow cytometry. Vδ1γδ T cells infiltrating in HCC were associated with better clinical outcome. Study in tumor micro-environment (TME) of HCC demonstrated that not total Vδ1γδ T but CD69+ Vδ1γδ subset infiltration was associated with smaller tumor volume. Moreover, HCC patients simultaneously with high TRDV1 and CD69 expression produced more effector molecules and had longer survival time. Since Vδ1γδ T cells in the tumor microenvironment were often difficult to access, we demonstrated that CD69+ Vδ1γδ T cells also existed in peripheral blood mononuclear cells (PBMC) of HCC and displayed enhanced cytotoxic potentials than HDs. Finally, we investigated the functions and found that CD69+ Vδ1γδ T cells exhibited stronger tumor reactivities when challenged by tumor cells. CD69+ Vδ1γδ T cells are functional Vδ1γδ T cell subsets in patients with HCC. Circulating CD69+ Vδ1γδ T cell is a promising candidate in immunotherapy of HCC. [Display omitted] • Vδ1γδ T associated with better clinical outcome of HCC. Higher CD69+ Vδ1γδ subset indicated smaller tumor. • CD69+ Vδ1γδ Tfrom PBMCs displayed enhanced cytotoxicity. [ABSTRACT FROM AUTHOR]

As a novel and promising antitumor target, AXL plays an important role in tumor growth, metastasis, immunosuppression and drug resistance of various malignancies, which has attracted extensive research interest in recent years. In this study, by employing the structure-based drug design and bioisosterism strategies, we designed and synthesized in total 54 novel AXL inhibitors featuring a fused-pyrazolone carboxamide scaffold, of which up to 20 compounds exhibited excellent AXL kinase and BaF3/TEL-AXL cell viability inhibitions. Notably, compound 59 showed a desirable AXL kinase inhibitory activity (IC 50 : 3.5 nmol/L) as well as good kinase selectivity, and it effectively blocked the cellular AXL signaling. In turn, compound 59 could potently inhibit BaF3/TEL-AXL cell viability (IC 50 : 1.5 nmol/L) and significantly suppress GAS6/AXL-mediated cancer cell invasion, migration and wound healing at the nanomolar level. More importantly, compound 59 oral administration showed good pharmacokinetic profile and in vivo antitumor efficiency, in which we observed significant AXL phosphorylation suppression, and its antitumor efficacy at 20 mg/kg (qd) was comparable to that of BGB324 at 50 mg/kg (bid), the most advanced AXL inhibitor. Taken together, this work provided a valuable lead compound as a potential AXL inhibitor for the further antitumor drug development. A class of novel AXL inhibitors has been discovered, in which compound 59 exhibited potent AXL inhibition, high kinase selectivity and significant in vivo anti-tumor efficacy with desirable pharmacokinetic profile. [Display omitted] [ABSTRACT FROM AUTHOR]

Natural products are essential sources of antitumor drugs. One such molecule, β -elemene, is a potent antitumor compound extracted from Curcuma wenyujin. In the present investigation, a series of novel 13,14-disubstituted nitric oxide (NO)-donor β -elemene derivatives were designed, with β -elemene as the foundational compound, and subsequently synthesized to evaluate their therapeutic potential against leukemia. Notably, the derivative labeled as compound 13d demonstrated a potent anti-proliferative activity against the K562 cell line, with a high NO release. In vivo studies indicated that compound 13d could effectively inhibit tumor growth, exhibiting no discernible toxic manifestations. Specifically, a significant tumor growth inhibition rate of 62.9% was observed in the K562 xenograft tumor mouse model. The accumulated data propound the potential therapeutic application of compound 13d in the management of leukemia. [ABSTRACT FROM AUTHOR]

• It was for the first time that we isolated aurantiamide acetate of high purity from the petroleum ether extract of 80% ethanol extract of P. capitatum. • Aurantiamide acetate could in inhibit the proliferation of various cancer cell types in vitro. • Aurantiamide acetate had a strong inhibitory effect on the proliferation of human gastric cancer BGC-823 cells, primarily by altering the cell cycle and promoting apoptosis. • Aurantiamide acetate significantly promoted the expression of Bax and Caspase-3 protein in BGC-823 cells. Aurantiamide acetate is a dipeptide derivative with antibacterial, antiviral, anti-inflammatory and analgesic activities. However, its antitumor activity has not been documented. This study aimed to prepare aurantiamide acetate from Polygonum capitatum and investigate its antitumor activity in vitro. The petroleum ether extract fraction of 80% ethanol extract from P. capitatum was separated by silica gel column chromatography. Aurantiamide acetate was obtained and identified by physicochemical properties, MS and NMR spectral data. The inhibitory effect of different doses of this compound on the proliferation of human umbilical vein endothelial cells (HUVECs), human gastric cancer BGC-823 cells, lung cancer A549 cells and colorectal cancer Caco-2 cells was detected by CCK-8 method. Morphological changes of BGC-823 cells were observed under the inverted microscope. The effect of aurantiamide acetate on BGC-823 apoptosis and cycle was detected by flow cytometry. The expression of Bax and caspase-3 in BGC-823 cells was detected by Western blotting. Aurantiamide acetate inhibited BGC-823, A549 and Caco-2 cell proliferation at the concentrations from 25 μmol/L to 100 μmol/L, but had no inhibitory effect on HUVECs at the concentrations from 12.5 μmol/L to 100 μmol/L. The inhibitory effect of Aurantiamide acetate was most pronounced on BGC-823 cell proliferation at IC 50 of 56.73 μmol/L, most probably by increasing the protein expression of caspase-3 and Bax in BGC-823 cells, and arresting cell cycle in G2/M phase. This is the first time that we isolated aurantiamide acetate from P. capitatum with a purity of 98.21%, and found that Aurantiamide acetate could in inhibit the proliferation of various cancer cell types in vitro. This finding may provide a new resource for developing anti-tumor drugs in future. [ABSTRACT FROM AUTHOR]

To expand the application of acylated blueberry pomace anthocyanins in food and nutraceuticals, their enzymatic acylation reaction and the cytotoxic response were explored. In this study, enzymatic acylation was carried out with cyanidin-3- O -glucoside (C3G) as the main body and Novozyme 435 as the biocatalyst. With a series of improvements, the reaction was carried out under the conditions of lauric acid as the acyl donor, tert-amyl alcohol as the reaction medium, the molar ratio of C3G to lauric acid of 1:10, the reaction time of 24 h and the reaction temperature of 60 °C, and 35.29 % acylation rate was obtained. Moreover, it was found that the lipophilicity, thermostability and photostability of the enzymatic acylated blueberry pomace anthocyanins were improved compared with the untreated blueberry pomace anthocyanins. Cytotoxicity studies showed that acylated blueberry pomace anthocyanins inhibited tumor cells (HeLa, HepG2, and B16 cells) significantly and were less toxic to normal cells (L929 cells) at the maximum concentration (1000 µg/mL) and the longest duration of action (72 h). This study established a method for acylation of blueberry pomace anthocyanins that may be applied to other natural sources of anthocyanins. [Display omitted] • The blueberry pomace was used as the raw material for extracting anthocyanins. • Acylation of anthocyanins using Novozym 435 lipase. • Enzymatic acylation improves the stability of anthocyanins. • The effect of acetylated anthocyanins on cell proliferation was studied. [ABSTRACT FROM AUTHOR]

In this study, a series of new C-14 amide substituted derivatives of dehydroabietic acid were designed, synthesized and evaluated for their anti-proliferative activity. Among them, compound 20 showed the best anti-proliferative activity against four tumor cell lines (A549, HepG2, MCF-7 and HCT-116), with half-maximal inhibitory concentration (IC 50) values ranging from 1.83 μM – 4.58 μM, which were approximately 2.72–6.26 times more potent than 5-fluorouracil (5-FU). Preliminary mechanistic studies suggested that 20 causes cell cycle arrest at the G2/M phase and induces apoptosis of HCT-116 tumor cells in a dose-dependent manner. Western blot analysis demonstrated that compound 20 induced this apoptosis through the intrinsic mitochondrial signaling pathway. These results suggested that abietic acid derivative 20 is a promising starting point for further optimization. [Display omitted] • potent in vitro antitumor activities. • Chemical stable and low toxicity. • Induction of apoptosis in cancer cells. [ABSTRACT FROM AUTHOR]

[Display omitted] Chalcone, a common chemical scaffold of many naturally occurring compounds, has been widely used as an effective template for drug discovery due to its broad biological activities. In this study, a series of chalcone derivatives were designed and synthesized based on the hybridization of 1-(2,4,6-trimethoxyphenyl)butan-1-one with chalcone. Interestingly, most of the target compounds exhibited inhibitory effect of tumor cells in vitro. Especially, (E)-3-(5-bromopyridin-2-yl)-1-(2,4,6-trimethoxyphenyl)prop-2-en-1-one (B3) revealed over 10-fold potency than 5-fluorocrail against the Hela and MCF-7 cells with IC 50 values of 3.204 and 3.849 μM respectively. Moreover, B3 displayed low toxicity on normal cells. Further experiments indicated that B3 effectively inhibited the proliferation and migration of tumor cells, and promoted their apoptosis. The calculation and prediction of ADME showed that the target compounds may have good pharmacokinetic properties and oral bioavailability. Reverse molecular docking suggested that the possible target of B3 is CDK1. Taken together, these results suggested that B3 appears to be a promising candidate that merits further attention in the development of anticancer drugs. [ABSTRACT FROM AUTHOR]

Green microalgae are a valuable source of biologically active substances with antitumor and antimicrobial effects. Coelastrella sp. BGV is a strain of green microalga isolated in Bulgaria. The aim of the study was to analyze the fatty acid profile of Coelastrella sp. BGV and to assess the antitumor and antimicrobial activities of the extracted free fatty acids. The fatty acid content of a total lipid extract from the green microalga Coelastrella sp. BGV was determined by gas chromatography mass spectrometry. The antitumor activity of FAs against human HeLa tumor cells was estimated by MTT testing and fluorescence microscopy methods. The antimicrobial activity of FAs against Gram-positive, Gram-negative bacteria and the fungal pathogen Candida albicans was studied by the disk diffusion and microdilution methods. Eleven fatty acids were identified in the lipid extract of Coelastrella sp. BGV, of which the monounsaturated oleic acid (18:1) was present in the largest amount - 31.7%, followed by the polyunsaturated linoleic acid (18:2) - 25.9% and saturated palmitic acid (16:0) - 19.2%. The ratio of total unsaturated to saturated fatty acids was 3:1, and the monounsaturated to polyunsaturated fatty acid ratio was 1:1. The extracted FAs showed statistically significant antiproliferative activity against HeLa tumor cells and induced morphological changes in the cell and nucleus characteristic of early and/or late apoptosis. FAs showed varying degrees of antibacterial and antifungal activity against Gram-positive, Gram-negative pathogens and C. albicans. The results obtained are promising in terms of the therapeutic potential of FAs from Coelastrella sp. BGV against tumor cells and against Gram-negative bacteria (Escherichia coli UPEC, Pseudomonas aeruginosa, Klebsiella pneumoniae) and the fungal pathogen Candida albicans. [Display omitted] • The fatty acid profile of green microalga strain Coelastrella sp. BGV was analyzed. • The antitumor and antimicrobial effects of the isolated fatty acids was assessed. • The lipid extract had a high content of unsaturated fatty acids. • The fatty acids inhibited the growth of HeLa tumor cells and induced apoptosis. • The fatty acids had antimicrobial and antifungal activity. [ABSTRACT FROM AUTHOR]

Platycodon grandiflorum is consumed popularly as a nutritional and healthy plant in East Asia, which has multiple medicinal functions. As an exploration to elucidate the beneficial ingredients, an acetylated glucomannan (PGP40-1) was purified from P. grandiflorum. Structural analysis showed that PGP40-1 was composed of →4)- β -Man p -(1→, →4)- β -Glc p -(1→, →6)- β -Glc p -(1→, and terminal α -Glc p -(1→. PGP40-1 was found to possess weak antitumor activity in vitro , which was thus modified to afford a selenized polysaccharide (Se-PGP40-1) by the HNO 3 /Na 2 SeO 3 method. Se-PGP40-1 showed significant antitumor activity in cell and zebrafish models, which could inhibit tumor proliferation and migration by inducing cell apoptosis and blocking angiogenesis. The research not only clarifies the ingredients of P. grandiflorum with high economical value, but also affords a potential antitumor agent originating from the plant polysaccharide. • An acetylated glucomannan (PGP40-1) was obtained from Platycodon grandiflorum. • PGP40-1 was modified for improving its antitumor activity. • Se-PGP40-1 exerted antitumor activity by inducing apoptosis. • Se-PGP40-1 showed antitumor activity in a zebrafish model. • Se-PGP40-1 had the ability to inhibit angiogenesis in a transgenic zebrafish model. [ABSTRACT FROM AUTHOR]

A series of piperine derivatives were designed and successfully synthesized. The antitumor activities of these compounds against 293 T human normal cells, as well as MDA-MB-231 (breast) and Hela (cervical) cancer cell lines, were assessed through the MTT assay. Notably, compound H7 exhibited moderate activity, displaying reduced toxicity towards non-tumor 293 T cells while potently enhancing the antiproliferative effects in Hela and MDA-MB-231 cells. The IC 50 values were determined to be 147.45 ± 6.05 μM, 11.86 ± 0.32 μM, and 10.50 ± 3.74 μM for the respective cell lines. In subsequent mechanistic investigations, compound H7 demonstrated a dose-dependent inhibition of clone formation, migration, and adhesion in Hela cells. At a concentration of 15 μM, its inhibitory effect on Hela cell function surpassed that of both piperine and 5-Fu. Furthermore, compound H7 exhibited promising antitumor activity in vivo, as evidenced by significant inhibition of tumor angiogenesis and reduction in tumor weight in a chicken embryo model. These findings provide a valuable scientific foundation for the development of novel and efficacious antitumor agents, particularly highlighting the potential of compound H7 as a therapeutic candidate for cervical cancer and breast cancer. [Display omitted] [ABSTRACT FROM AUTHOR]

Four new lignans named cephaliverins A–D (1 – 4), along with seven known analogues (5 – 11), were isolated from Cephalotaxus oliveri Mast. Their structures were elucidated on the basis of HR-ESI-MS and NMR analyses, and their absolute configurations were determined by ECD comparison. Cephaliverin A (1), herpetotriol (5) and hedyotol A (6) exhibited moderate antitumor activity against HepG2 and A549 cell lines. The manuscript covered four undescribed lignans along with seven known ones from Cephalotaxus oliveri , and the compounds were investigated for antitumor activity against HepG2 and A549 cells. [Display omitted] [ABSTRACT FROM AUTHOR]

The effect of ultrasonic intensity (28.14, 70.35, and 112.56 W/cm2) on Lignosus rhinocerotis polysaccharide (LRP) degraded by ultrasound assisted H 2 O 2 /Vc system (U-H/V) was investigated. U-H/V broke the molecular chain of LRP and improved the conformational flexibility, decreasing the molecular weight, intrinsic viscosity ([ η ]) and particle size. The functional groups and hyperbranched structure of LRP were almost stable after U-H/V treatment, however, the triple helix structure of LRP was partially disrupted. With increasing ultrasonic intensity, the critical aggregation concentration increased from 0.59 mg/mL to 1.57 mg/mL, and the hydrophobic microdomains reduced. Furthermore, the LRP treated with U-H/V significantly inhibited HepG2 cell proliferation by inducing apoptosis. The increase in antitumor activity of LRP was closely associated with the reduction of molecular weight, [ η ], particle size and hydrophobic microdomains. These results revealed that U-H/V treatment facilitates the degradation of LRP and provides a better insight into the structure-antitumor activity relationship of LRP. [Display omitted] • Ultrasound-assisted H 2 O 2 /Vc system (U-H/V) exhibited favorable degradation on LRP. • U-H/V broke the molecular chain of LRP and improved the conformational flexibility. • U-H/V disrupted part of the helical structure of LRP. • Hydrophobic microdomains of LRP decreased with increasing ultrasonic intensity. • The antitumor activity of LRP was improved after U-H/V treatment. [ABSTRACT FROM AUTHOR]

• The bioactivity mechanism of germanotungstate is still not well understood. • Two new Keggin-type germanotungstates were synthesized and crystallized. • Compound 1 and 2 exhibited high anti-proliferative activities against cancer cells. • Compounds 1 and 2 repressed the activity of STAT3 and Bcl-2. • Compounds 1 and 2 induced mitochondria-mediated apoptosis. Germanotungstates have been studied variously and widely in antitumor activity aganist various cancer cells; however, their mode of action remains unclear. In this study, we integrated transition metals and organic ligands into the Keggin polyoxometalates via covalence and metal coordination and crystallized two Keggin-type germanotungstates compounds 1 [Mn(2,2ʹ-bpy) 3 ] 2 [GeW 12 O 40 ]·0·5H 2 O and 2 [Fe(2,2ʹ-bpy) 2 Cl 2 ] 2 (Hbpy) 2 [GeW 12 O 40 ]. Compounds 1 and 2 exhibited high anti-proliferative activities against gastric cancer AGS and MGC803, colon cancer SW480, and liver cancer HepG2 cells, with IC 50 values below 50 μmol/L. Further investigation of the molecular mechanism in AGS cells revealed that compounds 1 and 2 repressed the STAT3 pathway and its downstream Bcl-2 family proteins. Downregulation of anti-apoptotic Bcl-2 family proteins leads to the dissipation of mitochondrial membrane potential, eventually triggering caspase-dependent apoptosis. These results demonstrate that compounds 1 and 2 exert antitumor activity via mitochondria-mediated apoptosis. Overall, our findings provide evidence for the development of antitumor germanotungstate-type drugs. [Display omitted] [ABSTRACT FROM AUTHOR]

• Seven novel 4-(tert -butyl)-5-(1,2,4-triazole-1-yl)thiazole derivatives containing benzoxazinone were synthesized. • The title compounds had certain antitumor activities against three cell lines MCF-7, Hela and A549, and compound B2 presented the most potent antitumor efficacy against A549. • Theoretical calculations were used to explain the possible bioactive sites and the stability of crystal structure, and the structure-activity relationship was proposed for further structural optimization. Seven novel 4-(tert -butyl)-5-(1 H -1,2,4-triazole-1-yl)thiazole derivatives containing benzoxazinone (B1-B7) were obtained by cyclization of 4-(tert -butyl)-5-(1 H -1,2,4-triazol-1-yl) -N- (2-hydroxy-benzyl)thiazol-2-amine. The chemical structures of the target compounds were confirmed by 1H NMR and 13C NMR. The single crystal X-ray diffraction revealed that B1 crystallizes in a triclinic system with the space group P 1 ¯. Hirshfeld surfaces and two dimensional (2D) fingerprint plots were employed to quantitatively characterize the influence of intermolecular interactions within the crystal lattice of B1. And the molecular electrostatic potential (MEP) surface was calculated employing Becke-3-Lee Yang Parr (B3LYP)/6-311++G (d,p) theoretical approach. Meanwhile, the Frontier-molecular orbitals of B1 and B2 were calculated using density functional theory (DFT) B3LYP technique with the def2-SVP basis set in the ground state. Preliminary biological tests revealed that the title compounds had certain antitumor activities against three cell lines MCF-7, Hela and A549, and compound B2 presented the most potent antitumor efficacy against A549. [ABSTRACT FROM AUTHOR]

• One-step synthesis of novel dibromothiazole derivative 2. • The chemical structure of thiazole 2 was characterized using X-ray analysis. • Based on Hirshfeld surface analysis, the crystal structure of dibromothiazole 2 exhibits the shortest intermolecular contacts at O1...H14A (2.548 Å), Br1...O1 (3.211 Å), and Br2...H7B (2.931 Å). • The thiazole 5a showed significant activity against Staphylococcus aureus, Salmonella SP., and Escherichia coli. Thiazole ring has a wide range of biological activities which is proven by its presence in more than eighteen FDA-approved drugs in addition to several compounds that are currently under clinical investigation. Substitution of the thiazole ring at positions 2,4, and 5 led to new derivatives with potent biological activities. Interestingly, the bromination of ethyl 2-cyano-2-(4-methyl-3-phenylthiazol-2(3H)-ylidene)acetate (1) in acetic acid afforded (Z)-ethyl 2-(5‑bromo-4-(bromomethyl)-3-phenylthiazol-2(3H)-ylidene)-2-cyanoacetate (2) instead of the expected bromomethyl derivative 3. The reaction of thiazole derivative 2 with p -anisidine or aniline produced the corresponding thiazole derivatives 5a,b. The synthesized compounds were characterized based on their spectral and elemental data. Moreover, the structure of compound 2 was determined through X-ray crystallography. The molecular structure of 2 was crystallized in the orthorhombic, Pna 2 1 , a = 15.8144 (6) Å, b = 9.0238 (4) Å, c = 11.3296 (4) Å, V = 1616.80 (11) Å3, Z = 4. Analysis of the d norm map and fingerprint plot for all possible intermolecular interactions in the crystal structure of thiazole 2 indicated the importance of the Br...O, O...H, and Br...H interactions in the molecular packing. The O1...H14A (2.548 Å), Br1...O1 (3.211 Å) and Br2...H7B (2.931 Å) interactions are the most short contacts. In addition, the percentages of the Br...O, O...H, and Br...H contacts are 2.3, 10.3 and 22.1 %, respectively. The antimicrobial activity of thiazole derivative 5a was tested, and the results revealed that it is equipotent to both Ampicillin against Staphylococcus aureus and to Gentamycin against Salmonella SP. In comparison to Doxorubicin, thiazole 5a showed less antitumor activity against the hepatocellular carcinoma (HepG-2) and colon carcinoma (HCT-116) cell lines. [ABSTRACT FROM AUTHOR]

• Enzymatic acylation of low purity anthocyanin extract with oleic acid. • Acylation rate of the reaction reached 54.3% at optimal conditions. • Oleic acid acylation improved antioxidant and antibacterial activities of product. • Acylated product showed potential antitumor activity. • Stability of product showed pH dependent behavior to various environments. Esterification of anthocyanins with saturated fatty acids have been widely investigated, while that with unsaturated fatty acids is little understood. In this study, crude extract (purity ∼ 35 %) of cyanidin-3- O -glucoside (C3G) from black bean seed coat was utilized as reaction substrate, and enzymatically acylated with unsaturated fatty acid (oleic acid). Optimization of various reaction parameters finally resulted in the highest acylation rate of 54.3 %. HPLC-MS/MS and NMR analyses elucidated the structure of cyanidin-3- O -glucoside-oleic acid ester (C3G-OA) to be cyanidin-3- O -(6″-octadecene)-glucoside. Introduction of oleic acid into C3G improved the lipophilicity, antioxidant ability, and antibacterial activity. Further, the color and substance stability analyses showed that the susceptibility of C3G and C3G-OA to different thermal, peroxidative, and illuminant treatments were highly pH dependent, which suggested individual application guidelines. Moreover, C3G-OA showed lower toxicity to normal cell (QSG-7701) and better inhibitory effect on the proliferation of HepG2 cells than C3G, which indicated its potential anti-tumor bioactivity. [ABSTRACT FROM AUTHOR]

[Display omitted] • Capecitabine (CTB) loaded potato starch (PS) and chitosan (CS) nanoparticles were made. • CTB-PS-CS-NPs characterized by TEM, SEM, DLS, FTIR, DSC, XRD, TGA, SERS. • CTB-PS-CS-NPs studied for in-vitro in HT-29 cells and in-vivo in DMH induced Balb/c mice. • To confirm biocompatibility and efficacy, haemolysis, crystal violet assay, ROS, histopathology conducted for CTB-PS-CS-NPs. • CTB-PS-CS-NPs evaluated by wound-healing, tube forming, and apoptosis studies, which confirm anticancer effects. Aggressive colon cancer treatment poses significant challenges. This study investigates the potential of innovative carbohydrate-based nanoparticles for targeted Capecitabine (CTB) delivery. CTB nanoparticles were synthesized by conjugating CTB with potato starch and chitosan using ultrasonication, hydrolysis, and ionotropic gelation. Characterization included drug loading, rheology, Surface-Enhanced Raman Spectroscopy (SERS), Fourier-Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD), and Thermogravimetric Analysis (TGA). In vitro and in vivo antitumor activity was evaluated using HT-29 cells and N, N-dimethylhydrazine-induced Balb/c mice, respectively. Cellular assays assessed angiogenesis, migration, proliferation, and apoptosis. Nanoparticles exhibited a mean size of 245 nm, positive zeta potential (+30 mV), high loading efficacy (76 %), and sustained drug release (92 % over 100 h). CTB-loaded nanoparticles displayed superior colon histology, reduced tumour scores, and inhibited VEGD and CD31 expression compared to free CTB. Cellular assays confirmed significant antitumor effects, including reduced tube formation, migration, and proliferation, and increased apoptosis. This study demonstrates the promise of CTB-loaded potato starch-chitosan nanoparticles for aggressive colon cancer treatment. These findings highlight the potential of these nanoparticles for further evaluation in diverse cancer models. [ABSTRACT FROM AUTHOR]

[Display omitted] Cancer continues to be a serious threat to human health worldwide. Lung, prostate and triple-negative breast cancers are amongst the most incident and deadliest cancers. Steroidal compounds are one of the most diversified therapeutic classes of compounds and they were proven to be efficient against several types of cancer. The epoxide function has been frequently associated with anticancer activity, particularly the 1,2-epoxide function. For this reason, three 1,2-epoxysteroid derivatives previously synthesised (EP1 , EP2 and EP3) and one synthesised for the first time (oxysteride) were evaluated against H1299 (lung), PC3 (prostate) and HCC1806 (triple-negative breast) cancer cell lines. A human non-tumour cell line, MRC-5 (normal lung cell line) was also used. EP2 was the most active compound in all cell lines with IC 50 values of 2.50, 3.67 and 1.95 µM, followed by EP3 with IC 50 values of 12.65, 15.10 and 14.16 µM in H1299, PC3 and HCC1806 cells, respectively. Additional studies demonstrated that EP2 and EP3 induced cell death by apoptosis at lower doses and apoptosis/necrosis at higher doses, proving that their effects were dose-dependent. Both compounds also exerted their cytotoxicity by ROS production and by inducing double-strand breaks. Furthermore, EP2 and EP3 proved to be much less toxic against a normal lung cell line, MRC5, indicating that both compounds might be selective, and they also demonstrated suitable in silico ADME and toxicity parameters. Finally, none of the compounds induced haemoglobin release. Altogether, these results point out the extreme relevance of both compounds, especially EP2 , in the potential treatment of these types of cancer. [ABSTRACT FROM AUTHOR]

Cancer has become one of the leading causes of death worldwide. It is urgent to develop new antitumor drugs with high efficiency and low toxicity. In this study, an inulin-type fructan CIP70-1 was purified and characterized from chicory and showed weak antitumor activity. To improve its antitumor effects, inulin-based selenium nanoparticles (CIP-SeNPs) were constructed and characterized. CIP-SeNPs were spherical nanoparticles (60 nm), which remained stable in water for more than 3 months. A cellular antitumor assay revealed that CIP-SeNPs had stronger inhibitory effects on cancer cells (MCF-7, A549, and HepG2) than CIP70-1 alone. Furthermore, the in vivo antitumor effects of CIP-SeNPs were confirmed using zebrafish models. The results showed that CIP-SeNPs significantly inhibited the proliferation and migration of tumors as well as the angiogenesis of transgenic zebrafish in the concentration range of 1–4 μg/mL. • An inulin fructan (CIP70–1) was purified and characterized from chicory. • An inulin-based selenium nanoparticle (CIP-SeNPs) was constructed and characterized. • CIP-SeNPs has good water-dispersion and excellent stability. • CIP-SeNPs blocked tumor proliferation and migration in the zebrafish model. • CIP-SeNPs inhibited angiogenesis in the transgenic zebrafish model. [ABSTRACT FROM AUTHOR]

Selenium nanoparticles (SeNPs) in an aqueous solution have poor stability and tend to aggregate when stored for a long time. In the present study, SeNPs were stabilized by using Lycium barbarum polysaccharide (LBP) and Lycium barbarum protein (LBPr) conjugates (LBPP) as a stabilizer and dispersing agent. Particularly, the LBPP 1 was obtained with subcritical water treatment. In addition, the physical stability, re-dispersity and antitumor activity of LBPP 1 -SeNPs were investigated. The results showed the particle size of LBPP 1 -SeNPs was maintained at 111.5–117 nm, which was stable at PH 6, 4 °C and darkness for at least 40 days. Besides, the result of TEM showed that the dispersion of LBPP 1 -SeNPs had more clear layers and smoother surfaces. Moreover, LBPP 1 -SeNPs had excellent re-dispersibility and exhibited a significant inhibitory effect on HepG-2 cells and Caco-2 cells, respectively (p < 0.05). Therefore, LBPP 1 -SeNPs can be used as potential selenium nutritional supplements for food and medical applications. • The Lycium barbarum polysaccharide-protein conjugates (LBPP 1) were obtained with subcritical water treatment. • Physicochemical and morphological characterization of the different SeNPs were compared. • LBPP 1 -SeNPs exhibited better stability. • LBPP 1 -SeNPs had good re-dispersibility and significant antitumor activity. [ABSTRACT FROM AUTHOR]

• FCN-411 had a manageable safety profile. • FCN-411 showed antitumor activity in EGFR TKI-treated, EGFR -mutated advanced NSCLC. • Patients without EGFR T790M achieved a greater ORR than those with this mutation. There are no approved epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for EGFR -mutated non-small cell lung cancer (NSCLC) without EGFR T790M mutation after progression on first- or second-generation EGFR-TKIs. We conducted this phase I, open-label, multicenter, dose-escalation/dose-expansion study to evaluate the safety, tolerability, antitumor activity, and pharmacokinetics of FCN-411, a TKI targeting EGFR, HER2, and HER4 , in patients with EGFR -mutated advanced NSCLC whose disease had progressed during treatment of EGFR-TKIs. Adult patients with stage IIIB–IV NSCLC harboring EGFR mutations (exon 18/19/20/21) who had progressed on prior EGFR-TKIs were enrolled. In the dose-escalation phase, patients received 4 mg, 8 mg, 12 mg, and 16 mg FCN-411 once daily until the maximum tolerated dose (MTD). In the dose-expansion phase, patients received FCN-411 at the recommended phase II dose (RP2D) continuously in 21-day cycles. The primary endpoints were safety, tolerability, MTD, and RP2D. From July 23, 2018 to September 29, 2020, 77 patients were enrolled, including 30 with EGFR T790M mutation in tumor tissues. The cut-off date was February 1, 2021. No dose-limiting toxicities were observed. The most common grade ≥ 3 treatment-emergent adverse events among all patients were diarrhea (8; 10.4%) and dermatitis acneiform (7; 9.1%). Ten of 67 evaluable patients achieved confirmed partial response, with an objective response rate (ORR) of 14.9% (95% confidence interval [CI], 8.3–24.0); the ORR was 33.3%, 14.0%, 0, and 25.0% at 4 mg, 8 mg, 12 mg, and 16 mg, respectively. Besides, the ORR in patients without and with EGFR T790M mutation was 20.5% and 7.4%, respectively. Moreover, 39 patients achieved stable disease across all doses, and the disease control rate was 73.1% (95% CI, 60.9–83.2). Median progression-free survival was 4.1 (95% CI, 2.9–5.3) months. Median duration of response and overall survival have not been reached. FCN-411 was well tolerated and demonstrated preliminary antitumor activity in patients with EGFR -mutated NSCLC after progression on EGFR-TKIs, especially in those without EGFR T790M mutation. The RP2D was defined as 8 mg once daily. Future studies are warranted. Trial registration: ClinicalTrials.gov, NCT03420079. [ABSTRACT FROM AUTHOR]

Glioblastoma (GB) is the most aggressive and prevalent glioma within the central nervous system. Despite considerable efforts, GB continues to exhibit a dismal 5-year survival rate (∼6%). This is largely attributed to unfavorable prognosis and lack of viable treatment options. Therefore, novel therapies centered around plant-derived compounds emerge as a compelling avenue to enhance patient survival and well-being. The South African species, Plectranthus hadiensis Schweinf. (P. hadiensis), a member of the Lamiaceae family, has a history of use in traditional medicine for treating a range of diseases, including respiratory, digestive, and liver disorders. This species exhibits diverse biological activities, such as anti-inflammatory and antitumoral properties, likely attributed to its rich composition of naturally occurring diterpenes, like the abietane diterpene, 7α-acetoxy-6β-hydroxyroyleanone (Roy). Roy has demonstrated promising antitumor effects in various cancer cell lines, making it a compelling candidate for further investigation into its mechanisms against GB. This study aims to investigate the antitumor activity and potential mechanism of Roy, a natural lead compound, in GB cells. Roy was isolated from the acetonic extract of P. hadiensis and its antitumor mechanism was assessed in a panel of human GB cell lines (U87, A172, H4, U373, and U118) to mimic tumor heterogeneity. Briefly, the impact of Roy treatment on the metabolic activity of cells was evaluated by Alamar Blue® assay, while cell death, cell cycle regulation, mitochondrial membrane potential, and activated caspase-3 activity were evaluated by flow cytometry. Measurement of mRNA levels of target genes was performed by qPCR, while protein expression was assessed by Western blotting. Cell uptake and impact on mitochondrial morphology were evaluated by confocal microscopy. Roy induced G 2 /M cell cycle arrest, mitochondrial fragmentation, and apoptosis by inhibiting the expression of anti-apoptotic proteins and increasing the levels of activated caspase-3. The concentrations of Roy needed to achieve significant inhibitory outcomes were notably lower (6–9 fold) than those of temozolomide (TMZ), the standard first-line treatment, for achieving comparable effects. In addition, at low concentrations (16 μM), Roy affected the metabolic activity of tumor cells while having no significant impact on non-tumoral cells (microglia and astrocytes). Overall, Roy demonstrated a robust antitumor activity against GB cells offering a promising avenue for the development of novel chemotherapeutic approaches. [Display omitted] • Roy, a diterpene isolated from P. hadiensis , has attractive antitumor properties. • Roy displayed better efficacy than temozolomide in glioblastoma cells. • Roy induced cell cycle arrest and apoptosis via activation of caspase-3. • Roy promoted alterations within the mitochondrial network. • Roy led to downregulation of oncogenes and decrease of Bcl-2 and p21 levels. [ABSTRACT FROM AUTHOR]

• The reaction of 1-phenylbutane-1,3‑dione with PhNCS and 1-chloropropan-2-one in the presence of NaOEt afforded thiophene 5 , whereas in K 2 CO 3 -DMF mixture yielded thiazole 11. • The synthesized compounds were characterized based on their spectral and x-ray structure analysis. • Possible intermolecular interactions were elucidated using Hirshfeld topology analysis. • Thiophene 5 showed significant antibacterial activity against Salmonella SP., escherichia coli , and moderate activity against Bacillus subtilis. • Compounds 5 and 11 showed weak cytotoxic effects on HCT-116 and HepG-2 carcinoma cell lines. A base-controlled chemoselective reaction of 1-phenylbutane-1,3‑dione with PhNCS and 1-chloropropan-2-one is described. Thiophene derivative 5 is obtained from the reaction in NaOEt solution, whereas thiazole 11 was isolated using potassium carbonate/DMF mixture. Spectral and X-ray structure analyses were used to characterize the synthesized compounds. Possible intermolecular interactions that control the molecular packing of the studied crystalline compounds were elucidated using Hirshfeld topology analysis. For thiophene 5 , the O...H contacts are the most important and contribute to 17.7 % of the whole predicted interactions. In the case of thiazole 11 , the C H...π and O...H non-covalent interactions are the most important contacts whereas the%C...H and%O...H contacts are 16.7 and 22.8 %, respectively. Additionally, there are some short H...H (47.0 %) interactions were detected where the H16A...H10A (2.165 Å) is the most important. The H...H interaction is the most dominant interaction which contributed by 47.0 and 47.0 % in 5 , and 11 , respectively. When compounds 5 and 11 were tested for their antimicrobial activity, the results revealed that thiophene derivative 5 has promising activity against both Salmonella SP. and Escherichia coli when compared to the standard medication gentamicin. Moreover, they were tested using the MTT assay for their antitumor activities against the colon carcinoma cell line (HCT-116) and the human hepatocellular carcinoma cell line (HepG-2). The results showed a lower cytotoxic effect against various cell lines in comparison to doxorubicin. [Display omitted] [ABSTRACT FROM AUTHOR]

Fifteen betulonic/betulinic acid conjugated with nucleoside derivatives were synthesized to enhance antitumor potency and water solubility. Among these, the methylated betulonic acid-azidothymidine compound (8c) exhibited a broad-spectrum of antitumor activity against three tested tumor cell lines, including SMMC-7721 (IC 50 = 5.02 μM), KYSE-150 (IC 50 = 5.68 μM), and SW620 (IC 50 = 4.61 μM) and along with lower toxicity (TC 50 > 100 μM) estimated by zebrafish embryos assay. Compared to betulinic acid (<0.05 μg/mL), compound 8c showed approximately 40-fold higher water solubility (1.98 μg/mL). In SMMC-7721 cells, compound 8c induced autophagy and apoptosis as its concentration increased. Transcriptomic sequencing analysis was used to understand the potential impacts of the underlying mechanism of 8c on SMMC-7721 cells. Transcriptomic studies indicated that compound 8c could activate autophagy by inhibiting the PI3K/AKT pathway in SMMC-7721 cells. Furthermore, in the xenograft mice study, compound 8c significantly slowed down the tumor growth, as potent as paclitaxel treated group. In conclusion, methylated betulonic acid-azidothymidine compound (8c) not only increases water solubility, but also enhances the potency against hepatocellular carcinoma cells by inducing autophagy and apoptosis, and suppressing the PI3K/Akt/mTOR signaling pathway. [Display omitted] • Conjugated triterpenes with nucleoside derivatives exhibited increased anti-tumor activity and solubility. • The methylated betulonic acid-azidothymidine derivative inducing autophagy and apoptosis in hepatocellular carcinoma cells. • Transcriptomic studies revealed its activation of autophagy by suppressing the PI3K/Akt/mTOR pathway in SMMC-7721 cells. [ABSTRACT FROM AUTHOR]

• Some progestins have a significant cytostatic action for various hormone-sensitive tumors. • The proliferative effects are highly dependent on the tumor microenvironment. • Dienogest, megestrol acetate and levonorgestrel increase the activity of NK-cells. • The immunosuppressive effects of hormonal drugs can complicate tumor treatment. Progestins are used to treat some hormone-sensitive tumors. This review discusses the mechanisms of progestins' effects on tumor cells, the differences in the effects of progesterone and its analogs on different tumor types, and the influence of progestins on the antitumor immune response. Progestins cause a cytostatic effect, but at the same time they can suppress the antitumor immune response, and this can promote the proliferation and metastasis of tumor cells. Such progestins as dienogest, megestrol acetate and levonorgestrel increase the activity of NK-cells, which play a major role in the body's fight against tumor cells. The use of existing progestins and the development of new drugs with gestagenic activity may hold promise in oncotherapy. [ABSTRACT FROM AUTHOR]

Polygonatum sibiricum , commonly known as Siberian Solomon's seal, is a traditional herb widely used in various traditional medical systems, especially in East Asia. In ancient China, the use of polygonatum sibiricum in medicine and food was mentioned in Li Shizhen's Bencao Gangmu of traditional Chinese medicine (TCM). It was also used in history of India in Vedic medicine. The plant is rich in bioactive substances such as polysaccharides, saponins, flavonoid and alkaloids. The aim of this review is to understand the pharmacological and pharmacokinetics research progress of the major components of polygonatum sibiricum , and to prospect its potential application and development in the treatment of various diseases. We conducted a systematic literature search against major online databases on the Web, including PubMed, ancient books, patents, PubMed, Wiley, Google Scholar, Web of Science, and others. We select the pharmacological process and mechanism of the main components of polygonatum sibiricum in a variety of diseases, and make a strict but careful supplement and in-depth elaboration to this review. Several studies have demonstrated the strong antioxidant properties of polygonatum extract, which can be attributed to the presence of flavonoids and other polyphenol compounds; for diabetes and other metabolic-related diseases, polygonatum saponins have particular advantages in regulating intestinal flora and lipoprotein concentration in organisms. In addition, the polysaccharides extracted from this plant have a strong anti-inflammatory effect, which is related to its ability to regulate proinflammatory cytokine and mediators. In the aspect of anti-tumor effect, polygonatum derivatives can induce cancer cell apoptosis mainly by adjusting the cell membrane potential and cell cycle. It is worth noting that the combined action of the main components of polygonatum also offers promising solutions for the treatment of the disease. Polygonatum polysaccharide has therapeutic effects on many diseases by adjusting cell signal pathways, polygonatum sibiricum have significant advantages in regulating intestinal flora, inducing apoptosis of tumor cells, activating antioxidant processes, etc. Further research and basic exploration are needed to prove the function and mechanisms of the main components of polygonatum sibiricum on related diseases. The study on the immunomodulatory properties of polygonatum revealed its potentiality of enhancing immune function, which made it an interesting subject for further exploration in the field of immunotherapy. Graphic abstract:Many compounds isolated from polygonatum sibiricum have anti-tumor activity, anti-oxidation activity, anti-inflammatory activity and metabolic regulation. [Display omitted] • Polygonatum sibiricum , including polygonatum polysaccharides, saponins and flavonoid, have a variety of pharmacological activities. • Polygonatum polysaccharide produces intracellular antioxidant activity through various signal pathway networks. • The methods of separation and purification of polygonatum sibiricum derivatives significantly affect their pharmacological properties and therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Honokiol (HNK) is a typical natural biphenyl polyphenol compound. It has been proven to have a wide range of biological activities, including pharmacological effects such as anti-cancer, anti-inflammatory, neuroprotective, and antimicrobial. However, due to the poor stability, water solubility, and bioavailability of HNK, HNK has not been used in clinical treatment. This article reviews the latest research on the pharmacological activity of HNK and summarizes the HNK derivatives designed and improved by several researchers. Reviewing these contents could promote the research process of HNK and guide the design of better HNK derivatives for clinical application in the future. [Display omitted] • HNK has various bioactivities, including anti-cancer, anti-inflammation, neuroprotective, and anti-microbial effects. • Various derivative compounds of HNK were discussed based on different classifications of pharmacological activity. • The structure-activity relationship (SAR) of HNK could guide the artificial modification of HNK. [ABSTRACT FROM AUTHOR]

Two bases-decavanadates coordination compounds [(C 6 H 13 N 4) 2 ][Mg(H 2 O) 6 ] 2 [O 28 V 10 ].6H 2 O (1) and [(C 7 H 11 N 2) 4 ][Mg(H 2 O) 6 ][O 28 V 10 ].4H 2 O (2) have been synthesized and well characterized using vibrational spectroscopy (infrared), UV–Visible analysis and single crystal X-ray diffraction technique. The formula unit, for both compounds, is composed by the decavanadate [V 10 O 28 ]6−, hydrated magnesium ion, a counter anion and free water molecules. The transition metal adopts octahedral geometries in both compound (1) and (2). The existence of a multitude of hydrogen bonding interactions for both compounds provides a stable three-dimensional supramolecular structure. Optical absorption reveals a band gap energy indicating the semi-conductive nature of the compound. In this study, the cytotoxic and the anti-proliferative activities of compounds (1) and (2) on human cancer cells (U87 and MDA-MB-231) were investigated. Both compounds demonstrated dose-dependent anti-proliferative activity on U87 and MDA-MB-231 with respective IC 50 values of 0.82 and 0.31 μM and 1.4 and 1.75 μM. These data provide evidence on the potential anticancer activity of [(C 6 H 13 N 4) 2 ][Mg(H 2 O) 6 ] 2 [O 28 V 10 ].6H 2 O and [(C 7 H 11 N 2) 4 ][Mg(H 2 O) 2 ][O 28 V 10 ].4H 2 O. Molecular docking of the compounds was also examined. Molecular docking studies were performed for both compounds against four target receptors and revealed better binding affinity with these targets in comparison to Cisplatin. Moreover, molecular docking investigations suggest that these compounds may function as potential inhibitors of proteins in brain and breast cells, exhibiting greater efficiency compared to Cisplatin. Novel decavanadate compounds were synthesized and characterized using single crystal X-ray diffraction. These compounds displayed potent cytotoxicity against human cancer cells. A molecular docking study revealed their binding affinity to key receptors in brain and breast cancer, offering promising avenues for advancing cancer treatment strategies through innovative chemical synthesis. [Display omitted] • Novel decavanadate compounds were synthesized and characterized. • The crystal structures were elucidated by single crystal X-ray diffraction method. • Evaluated cytotoxic, anti-proliferative effects for the synthesized compounds was studied. • The molecular docking studies were performed on the decavanadate compounds. [ABSTRACT FROM AUTHOR]

[Display omitted] • Preparation of tannin films by low-energy electron beam deposition. • Modification of titanium substrates with tannin films is stable, one-step, and economical. • Tannin films in PBS have a slow-release effect that facilitates the inhibition of tumor recurrence over a relatively long period of time. • Tannin film has excellent bone tumor inhibitory activity and promotes bone tumor apoptosis. Osteosarcoma is a prevalent malignant bone tumor and incomplete surgical resection of the tumor often results in higher rates of local recurrence. To tackle this issue, there is an urgent requirement to develop implants that possess the capability to inhibit tumor recurrence. In this paper, we prepared three different thicknesses of tannin (TA) films on titanium substrates using low-energy electron beam deposition to study their effects on bone tumor inhibition. The structure and morphology of TA films were analyzed by FT-IR, XPS, SEM, and EDX. The release kinetics of tannins were investigated, revealing their ability to achieve sustained release. This sustained release is advantageous for long-term inhibition of bone tumors. Cellular experiments, including cytotoxicity test, live/dead double staining, cell migration and western blot, were performed to evaluate the tumor-suppressing activity of TA films in vitro. The results indicated that the TA films were not only non-cytotoxic to normal bone cells, but also exhibited excellent in vitro anti-tumor activity by effectively inhibiting the activity and migration of bone tumor cells. [ABSTRACT FROM AUTHOR]

An undisclosed polysaccharide, BCP80–2, was isolated from Belamcanda chinensis (L.) DC. Structural investigation revealed that BCP80–2 consists of ten monosaccharide residues including t- α -Ara f -(1→, →3,5)- α -Ara f -(1→, →5)- α -Ara f -(1→, →4)- β -Xyl p -(1→, →3)- α -Rha p -(1→, →4)- β -Man p -(1→, t- β -Glc p -(1→, →6)- α -Glc p -(1→, t- β -Gal p -(1→, and→3)- α -Gal p -(1→. In vivo activity assays showed that BCP80–2 significantly suppressed neoplasmic growth, metastasis, and angiogenesis in zebrafish. Mechanistic studies have shown that BCP80–2 inhibited cell migration of HepG2 cells by suppressing the FAK signaling pathway. Moreover, BCP80–2 also activated immunomodulation and upregulated the secretion of co-stimulatory molecules CD40, CD86, CD80, and MHC-II. In conclusion, BCP80–2 inhibited tumor progression by targeting the FAK signaling pathway and activating CD40-induced adaptive immunity. [Display omitted] [ABSTRACT FROM AUTHOR]

Etoposide liposomes (VP16-LPs) incorporating DSPE-mPEG2000 were prepared and further made into freeze-dried powder. After intravenous injection, VP16-LPs enhanced antitumor effects on small cell lung cancer and reduced toxicity of drugs compared with marketed VP16 injection. [Display omitted] Etoposide (VP16) is commonly used in the treatment of small cell lung cancer (SCLC) in clinical practice. However, severe adverse reactions such as bone marrow suppression toxicity limit its clinical application. Although several studies on VP16 liposomes were reported, no significant improvement in bone marrow suppression toxicity has been found, and there was a lack of validation of animal models for in vivo antitumor effects. Therefore, we attempted to develop a PEGylated liposomal formulation that effectively encapsulated VP16 (VP16-LPs) and evaluated its therapeutic effect and toxicity at the cellular level and in animal models. First, we optimized the preparation process of VP16-LPs using an orthogonal experimental design and further prepared them into freeze-dried powder to improve storage stability of the product. Results showed that VP16-LPs freeze-dried powder exhibited good dispersibility and stability after redispersion. In addition, compared to marketed VP16 injection, VP16-LPs exhibited sustained drug release characteristics. At the cellular level, VP16-LPs enhanced the cellular uptake of drugs and exhibited strong cytotoxic activity. In animal models, VP16-LPs could target and aggregate in tumors and exhibit a higher anti-tumor effect than VP16-injection after intravenous injection. Most importantly, hematological analysis results showed that VP16-LPs significantly alleviated the bone marrow suppression toxicity of drug. In summary, our study confirmed that PEGylated liposomes could enhance therapeutic efficacy and reduce toxicity of VP16, which demonstrated that VP16-LPs had enormous clinical application potential. [ABSTRACT FROM AUTHOR]

• A novel SHP2 inhibitor was designed and synthesized for the first time. • The targeted compound was calculated for its optimized structures by DFT. • The structures optimized by a DFT method were compared with the X-ray structures. • Molecular docking and antitumor activity test indicated that it had potential inhibitory effect. • The targeted compound of vibrational frequencies was analyzed. N -(3-((1-(3-Bromo-4-fluorophenyl)-5-oxo-[1,2,4]triazolo[4,3- a ]quinazolin-4(5 H) -yl)methyl)phenyl)but‑3-enamide, as a potential SHP2 inhibitor, was synthesized via an eight-step reaction, and its structure was characterized by spectroscopy. The single crystal structure of the compound was determined by X-ray diffraction, and density functional theory (DFT) was used to calculate the optimal structure of the target molecule, which was in agreement with the crystal structure as determined by single-crystal diffraction. The molecular electrostatic potentials and frontier molecular orbitals were analyzed using the B3LYP/6–311+ G (2d, p) method. In addition, Hirshfeld surface analysis, molecular docking, and anticancer activity studies were performed on the title compound. The results showed that the title compound had a good inhibitory activity against SHP2. [Display omitted] [ABSTRACT FROM AUTHOR]

Protein arginine methyltransferase 5 (PRMT5) and epidermal growth factor receptor (EGFR) are both involved in the regulation of various cancer-related processes, and their dysregulation or overexpression has been observed in many types of tumors. In this study, we designed and synthesized a series of 1-phenyl-tetrahydro-β-carboline (THβC) derivatives as the first class of dual PRMT5/EGFR inhibitors. Among the synthesized compounds, 10p showed the most potent dual PRMT5/EGFR inhibitory activity, with IC 50 values of 15.47 ± 1.31 and 19.31 ± 2.14 μM, respectively. Compound 10p also exhibited promising antiproliferative activity against A549, MCF7, HeLa, and MDA-MB-231 cell lines, with IC 50 values below 10 μM. Molecular docking studies suggested that 10p could bind to PRMT5 and EGFR through hydrophobic, π-π, and cation-π interactions. Furthermore, 10p displayed favorable pharmacokinetic properties and oral bioavailability (F = 30.6%) in rats, and administrated orally 10p could significantly inhibit the growth of MCF7 orthotopic xenograft tumors. These results indicate that compound 10p is a promising hit compound for the development of novel and effective dual PRMT5/EGFR inhibitors as potential anticancer agents. [Display omitted] • Novel 1-phenyl-THβC derivatives were evaluated as first dual PRMT5/EGFR inhibitors. • Some derivatives significantly inhibited the proliferation of several cancer cell lines. • Compound 10p showed the best dual inhibition on PRMT5 and EGFR, and promising antiproliferative activity. • Compound 10p displayed favorable in vivo PK and PD properties. [ABSTRACT FROM AUTHOR]

In this study, we extracted and isolated two polysaccharides with molecular weights of 2.28 × 104 Da and 2.71 × 103 Da from Cordyceps militaris , named CMP-90 and CMP-E, respectively. Structural characterization revealed that CMP-90 consists of six glycosidic bonds, Glc p -(1→, Gal p -(1→, →3)-Glc p -(1→, →6)-Glc p -(1→, Man p -(1→, and →4,6)-Man p -(1→. CMP-E consists of →4)-Gal p -(1→, →4)-Glc p -(1→, →6)-Glc p -(1→, Glc p -(1→, →3)-Glc p -(1→, →2,3,6)-Glc p -(1→, and →2)-Glc p -(1→ glycosidic bonds. Animal experiments demonstrated that both polysaccharides were able to increase immune cell viability, regulate the ratio of lymphocyte subpopulations, and increase the levels of serum cytokines (TNF-α, IL-2, and IFN-γ) by improving the status of immune organs in loaded tumor-bearing mice. CMP-90 and CMP-E were also able to activate caspase-mediated apoptosis to cause apoptosis of S180 cells through the Wnt/β-catenin pathway, which was blocked at the G1 phase. The above experimental results suggest that Cordyceps militaris polysaccharides have the potential to become a functional agent for sarcoma. [Display omitted] • CMP-90 and CMP-E were purified from Cordyceps militaris. • The structures of the two Cordyceps militaris polysaccharides were compared. • CMP-90 and CMP-E presented superior anti-tumor activity in vivo. • C. militaris polysaccharides induces cell apoptosis through Wnt/β-catenin pathway. [ABSTRACT FROM AUTHOR]

Cyclometalated Ir(III) complex [Ir(L) 2 (dppz)]PF 6 (where L = 1-methyl-2-(thiophen-2-yl)-1H-benzo[ d ]imidazole and dppz = dipyrido [3,2- a :2′,3′- c ]phenazine) (Ir1) is potent anticancer agent whose potency can be significantly increased by irradiation with blue light. Structural features of the cyclometalated Ir(III) complex Ir1 investigated in this work, particularly the presence of dppz ligand possessing an extended planar area, suggest that this complex could interact with DNA. Here, we have shown that Ir1 accumulates predominantly in mitochondria of cancer cells where effectively and selectively binds mitochondrial (mt)DNA. Additionally, the results demonstrated that Ir1 effectively suppresses transcription of mitochondria-encoded genes, especially after irradiation, which may further affect mitochondrial (and thus also cellular) functions. The observation that Ir1 binds selectively to mtDNA implies that the mechanism of its biological activity in cancer cells may also be connected with its interaction and damage to mtDNA. Further investigations revealed that Ir1 tightly binds DNA in a cell-free environment, with sequence preference for GC over AT base pairs. Although the dppz ligand itself or as a ligand in structurally similar DNA-intercalating Ru polypyridine complexes based on dppz ligand intercalates into DNA, the DNA binding mode of Ir1 comprises surprisingly a groove binding rather than an intercalation. Also interestingly, after irradiation with visible (blue) light, Ir1 was capable of cleaving DNA, likely due to the production of superoxide anion radical. The results of this study show that mtDNA damage by Ir1 plays a significant role in its mechanism of antitumor efficacy. In addition, the results of this work are consistent with the hypothesis and support the view that targeting the mitochondrial genome is an effective strategy for anticancer (photo)therapy and that the class of photoactivatable dipyridophenazine Ir(III) compounds may represent prospective substances suitable for further testing. [Display omitted] • Photoactivatable dipyridophenazine Ir(III) complex Ir1 is potent anticancer agent. • Ir1 accumulates in mitochondria of cancer cells and damages mitochondrial DNA. • DNA binding mode of Ir1 comprises a groove binding. • After irradiation with visible (blue) light, Ir1 is capable of cleaving DNA. • Ir1 effectively suppresses transcription of mitochondria-encoded genes. [ABSTRACT FROM AUTHOR]

The green synthesis of metal nanoparticles (NPs) using plant derivatives and microbial organisms has emerged as a significant avenue for sustainable materials science. This review provides an overview of eco-friendly methods for synthesizing metal NPs, particularly emphasizing their synthesis from plant biomass using rapid and environmentally friendly approaches. The variation in reduction mechanisms among different plant species, an underexplored aspect, is thoroughly discussed. The review highlights the diverse applications of green-synthesized metal NPs in biomedicine, particularly their exceptional antimicrobial and antioxidant properties, rendering them attractive for wastewater treatment – an area of increasing interest. It covers various synthesis and characterization routes, and functional properties of metal NPs, along with presenting successful proof-of-concept examples. A fundamental exploration of their physical morphology is provided, contributing to a multidisciplinary approach to environmental research. The review also sheds light on current trends in water treatment techniques, with a specific focus on the application of NPs synthesized through green methods, aligning with the broader aim to understand and address environmental challenges more holistically. Given the limited data and growing industrial demand for plant-mediated metal NPs, this review aims to inspire readers from diverse disciplines to explore the potential of naturally synthesized NPs and their expanding applications, contributing to the advancement of sustainable materials science. [Display omitted] • Green synthesis of metal NPs for wastewater treatment: recent progress and developments. • Role of plant derivatives and microbes in green NPs synthesis for biomedical applications. • Importance of size, shape, and geometrical parameters in green NPs synthesis for water treatment. • State-of-the-art functional properties of green NPs: antimicrobial, antioxidant, anticancer. [ABSTRACT FROM AUTHOR]

The development and application of new natural selenium polysaccharides with relatively clear structure and excellent activity have become hot and difficult issues. This study used GC–MS and 2D NMR to characterize the detailed chain structure information of selenium polysaccharide (Se-POP-3) from Selenium-enriched Pleurotus ostreatus , and then explored its anti-gastric cancer and anti-colon cancer effects in vitro. Results showed that the main chain of Se-POP-3 was →[3)-β-D-Glcp-(1] 2 → 6)-β-D-Glcp-(1 → 3,6)-β-D-Glcp-(1 → 3)-β-D-Glcp-(1→, and the branch was α-D-Glcp-(1 → [4)-α-D-Glcp-(1] 4 →, which was connected to the main chain through the O-3 bond of →3,6)-β-D-Glcp-(1 → glycosidic bond. In addition, Se-POP-3 could reduce viability, induce apoptosis, inhibit migration and invasion, destroy the Bax/Bcl-2 ratio, and inhibit the epithelial-to-mesenchymal transition of MGC-803 and HCT-116 cells in vitro. Moreover, this study also showed that within the concentration range set in this study, Se-POP-3 had no significant effect on the growth of normal cells (NCM460 cells). This study can provide a theoretical basis for the potential application of Se-POP-3 as an anti-gastrointestinal cancer drug or functional food. [ABSTRACT FROM AUTHOR]

Bacillus thuringiensis (Bt) is a ubiquitous bacterium that produces several proteins that are toxic to different invertebrates such as insects, nematodes, mites, and also some protozoans. Among these, Cry and Cyt proteins are most explored as biopesticides for their action against agricultural pests and vectors of human diseases. In 2000, a group of researchers from Japan isolated parasporal inclusion proteins from B. thuringiensis , and reported their cytotoxic action against human leukemia. Later, other proteins with similar antitumor properties were also isolated from this bacterium and these cytotoxic proteins with specific activity against human cancer cells were named parasporins. At present, nineteen different parasporins are registered and classified in six families. These parasporins have been described to have specific in vitro antitumor activity against several cancer cell lines. The antitumor activity makes parasporins possible candidates as anticancer agents. Various research groups around the world are involved in isolating and characterizing in vitro antitumor activity of these proteins and many articles reporting such activities in detail have been published. However, there are virtually no data regarding the antitumor activity of parasporins in vivo. This review summarizes the properties of these potentially useful antitumor agents of natural origin, focusing on their in vivo activity thus also highlighting the importance of testing these proteins in animal models for a possible application in clinical oncology. [Display omitted] • Bacillus thuringiensis produces several proteins that are toxic to different invertebrates. • Parasporins are proteins with similar antitumor properties. • Parasporins have specific in vitro antitumor activity against several cancer cell lines. • No data exist regarding the antitumor activity of parasporins in vivo. • Antitumor activity makes parasporins possible candidates as anticancer agents. [ABSTRACT FROM AUTHOR]

We recently isolated a polysaccharide from Polygala tenuifolia Willd. (PTP) and reported that such a PTP could induce cell apoptosis with FAS/FAS-L-mediated death receptor pathway in human lung cancer cells. Herein, we indicate antitumor activity and immunoregulation of PTP for S180 sarcoma cells by in vitro and in vivo targeting. In vitro , S180 cells took on prominent characteristics of apoptosis under-treated with PTP in follow-up antitumor activity studies, including irregular shrinkage and fragmentation nuclear, apoptotic bodies formation, and reduction of mitochondrial membrane potential (MMP). Additionally, flow cytometry indicated that the number of normal cells (FITC−/PI−) gradually decreased from 98.08% to 16.31%, while the number of apoptotic cells (FITC+/PI− or FITC+/PI+) increased from 0.87% to 54.84%. The ratio of BAX and Bcl-2 increased, which promoted the release of Cytochrome C (Cyt C), and it further maximized the expression of activated-caspase-9/−3. Additionally, the PTP revised the immune organ indexes, the activities of NK cells and lymphocytes, and induced the secretion of IL-2 (7.34–16.17%), IFN-γ (14.34–20.85%) and TNF-α (12.32–22.58%) in vivo. Thus, PTP can induce cell apoptosis and activate the immunoregulation mechanism thereby exhibiting biological activity. [Display omitted] [ABSTRACT FROM AUTHOR]

Onconase (ONC) is a monomeric amphibian "pancreatic-type" RNase endowed with remarkable anticancer activity. ONC spontaneously forms traces of a dimer (ONC-D) in solution, while larger amounts can be formed when ONC is lyophilized from mildly acidic solutions. Here, we report the crystal structure of ONC-D and analyze its catalytic and antitumor activities in comparison to ONC. ONC-D forms via the three-dimensional swapping of the N-terminal α-helix between two monomers, but it displays a significantly different quaternary structure from that previously modeled [Fagagnini A et al., 2017, Biochem J 474, 3767-81], and based on the crystal structure of the RNase A N-terminal swapped dimer. ONC-D presents a variable quaternary assembly deriving from a variable open interface, while it retains a catalytic activity that is similar to that of ONC. Notably, ONC-D displays antitumor activity against two human melanoma cell lines, although it exerts a slightly lower cytostatic effect than the monomer. The inhibition of melanoma cell proliferation by ONC or ONC-D is associated with the reduction of the expression of the anti-apoptotic B cell lymphoma 2 (Bcl2), as well as of the total expression and phosphorylation of the Signal Transducer and Activator of Transcription (STAT)-3. Phosphorylation is inhibited in both STAT3 Tyr705 and Ser727 key-residues, as well as in its upstream tyrosine-kinase Src. Consequently, both ONC species should exert their anti-cancer action by inhibiting the pro-tumor pleiotropic STAT3 effects deriving either by its phospho-tyrosine activation or by its non-canonical signaling pathways. Both ONC species, indeed, increase the portion of A375 cells undergoing apoptotic cell death. This study expands the variety of RNase domain-swapped dimeric structures, underlining the unpredictability of the open interface arrangement upon domain swapping. Structural data also offer valuable insights to analyze the differences in the measured ONC or ONC-D biological activities. [ABSTRACT FROM AUTHOR]

A strategy by exogenous addition of quorum sensing molecule farnesol to improve the production, antioxidant activity and antitumor activity of extracellular polysaccharide (EPS) of Grifola frondosa by liquid fermentation was proposed in the study. The highest yield of EPS induced by farnesol was 1.25 g/L, which was 150% higher than that of the control. Four polysaccharides including EPS-C-0M, EPS-C-0.2M, EPS-F-0M and EPS-F-0.2M were extracted and purified under the conditions of control and farnesol respectively. The physicochemical properties, antioxidant activities and antitumor activities were studied. Their chemical composition differed in sugar, protein and uronic acid contents, and they were composed of six constituent monosaccharides with different ratios, with the average molecular weights of 1.12 × 103, 1.89 × 103, 1.41 × 103 and 2.02 × 103 kDa, respectively. They presented similar FT-IR spectra, but different surface morphology. Antioxidant experiments showed that they had strong scavenging activities on ABTS+, hydroxyl radical, O2− and DPPH radical. Antitumor experiments showed that they had strong inhibitory effects on human cervical cancer (HeLa) cells and human liver cancer cells (HepG 2) cells. Among the four polysaccharides, EPS-F-0.2M showed the highest antioxidant and antitumor activities, indicating that farnesol could regulate the biological activity of EPS by affecting structure and properties. These results demonstrated that appropriate adjustment of culture conditions had potential application in the development of polysaccharides with high antioxidant and antitumor activity. It provided a new strategy to enhance the production and bioactivity of edible and medicinal fungal polysaccharides by using quorum sensing molecules. [ABSTRACT FROM AUTHOR]

Flavonols are one of the most promising class of bioactive compounds belonging to the broad family of the flavonoids, characterized by a unique set of features in their basic chemical skeleton and several specific substitutions in selected position of the rings A, B and C. This interesting class of phytochemicals includes compounds such as quercetin, kaempferol, myricetin, rhamnetin, morin, fisetin, galagin, azaleatin and their respective glycosyl derivatives. They have been identified in several foods and provide them great health benefits. This review updates and integrates, in a critical fashion, the current knowledge on flavonols as food sources, chemical features, structure-activity relationships, bioavailability and health benefits (from preclinical and clinical studies), focusing on both in vitro and in vivo reports. Dietary flavonols are bioavailable molecules in human with impressive health benefits (such as antioxidation, cardioprotection, antibacterial, antiviral and anticancer activity) and the process of metabolization also produces compounds with remarkable bioactivities just like the corresponding precursors. Their inclusion into human diet is highly recommended for their unquestionable health promoting properties, being excellent nutraceuticals as well as ingredients for good functional food. [Display omitted] • Food flavonols are nutraceuticals with remarkable biological applications. • Basic skeleton of flavonols has characteristic features for their functionality. • Some foods in the human diet are very rich source of flavonols. • Flavonols have promising anticancer, antimicrobial, antioxidant and antiviral properties. [ABSTRACT FROM AUTHOR]

A polysaccharide from the aqueous extract of Boletus aereus fruit (BAP) was isolated. The antitumor activities of BAP and/or cyclophosphamide (CTX) were investigated using the model of S180 tumor-bearing mice. Results indicated that BAP could effectively inhibit the growth of S180 solid tumors and protect the immune organs. Hematoxylin and eosin staining, Annexin V-FITC/PI staining, and mitochondrial membrane potential analysis demonstrated that BAP could induce the apoptosis of S180 tumor cells. In combination with CTX, BAP exhibited a significant synergistic antitumor effect on S180 cells. Furthermore, a novel polysaccharide, namely, BAPF, was purified from BAP by using DEAE Cellulose-52 column and Sephadex G-100 gel column. Structural characterization revealed that BAPF was primarily composed of mannose, glucuronic acid, glucose, galactose, arabinose, and fucose at a proportion of 12.98:1:16.8:16.48:1.08:9.1. Its average molecular weight was 1.79 × 106 Da. FTIR and NMR analyses demonstrated that BAPF was a pyranose with α-type and β-type glycosidic residues. [ABSTRACT FROM AUTHOR]

Selenium nanoparticles (SeNPs), a potential cancer therapeutic agent, have attracted widespread attention owing to their high bioavailability and remarkable anticancer activity. Nevertheless, the poor water solubility and dispersibility of SeNPs seriously limit their applications. In the present study, we synthesized stable and individual spherical selenium nanoparticles (CL90-Tw-SeNP2) with an average diameter of approximately 79 nm using a polysaccharide extracted from Citrus limon (CL90) and Tween-80 as the decorator and stabilizers. The proportion of selenium in CL90-Tw-SeNP2 was 10.6%. CL90-Tw-SeNP2 possessed high stability and good dispersion in water for more than three months. The subsequent biological assay revealed that CL90-Tw-SeNP2 showed remarkable antitumor effects against HepG2 cells, with an IC 50 value of 49.13 μg/mL, by inducing cell apoptosis. Furthermore, an in vivo zebrafish assay to explore possible applications indicated that CL90-Tw-SeNP2 could inhibit the proliferation and migration of tumors and the zebrafish angiogenesis. These results indicated that CL90-Tw-SeNP2 could be a potential agent for cancer treatment, especially against human liver hepatoma cancer. [Display omitted] • High stability and selenium content of CL90-Tw-SeNP2 were synthesized successfully. • Citrus limon polysaccharides and Tween-80 acted as the stabilizers in the reaction. • CL90-Tw-SeNP2 exerted remarkable antitumor effects by inducing apoptosis. • CL90-Tw-SeNP2 inhibited the proliferation and migration of tumors. • CL90-Tw-SeNP2 can block the angiogenesis of zebrafish. [ABSTRACT FROM AUTHOR]

Production of polysaccharides by white-rot-fungi in submerged cultivation has several advantages due to process control. This work deals with the submerged cultivation, extraction and antitumor activity of polysaccharides from a wild strain of Schizophyllum radiatum isolated from a tropical forest of Colombia. The mushroom was cultivated in laboratory conditions, and classified by classical and molecular taxonomy. Submerged cultivation was performed in a bioreactor of 5 L using a ligninolytic residue as substrate. The fermentation conditions were 30 ± 1 °C, pH 4.5, 300 rpm and 1.5 vvm of air for 4 days. The yields were 16.8 g/L (w / v) of biomass, and after extraction, 0.6 g/L of water-soluble exopolysaccharide (SEPS) and 2.01 % (w /w) of water-soluble intrapolysaccharide (SIPS) were obtained. In each extract total carbohydrate, glucans and protein contents were determined. Also, nuclear magnetic resonance (NMR), scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, X-ray diffractometry (XRD), high performance liquid chromatography with refraction index detection (HPLC-RI), high performance gel permeation chromatography (HPGPC) and Nuclear Magnetic Resonance (NMR) analysis were performed. Results indicated that SEPS and SIPS are heteropolysaccharides with amorphous structure and high molecular weights. Antitumor and immunostimulant activity was evaluated in different cancer cell lines. The results suggest these polysaccharides have direct and indirect antitumor activity activating immune cells such as macrophages. These findings enhance our knowledge about new sources of fungal metabolites that serve as adjuvant, cheaper and less harmful alternatives to cancer treatment. [Display omitted] • Phylogenetic analysis classified the wild mushroom isolated as Schizophyllum radiatum. • Intra- and exo polysaccharides of S. radiatum were produced in submerged cultivation on a bioreactor scale. • Water-soluble heteropolysaccharides from S. radiatum were isolated and characterized. • S. radiatum heteropolysaccharides showed antitumor and immunostimulant activities in vitro. [ABSTRACT FROM AUTHOR]

Natural products are one of the important sources for the discovery of new drugs. Betulinic acid (BA), a pentacyclic triterpenoid widely distributed in the plant kingdom, exhibits powerful biological effects, including antitumor activity against various types of cancer cells. A considerable number of BA derivatives have been designed and prepared to remove their disadvantages, such as poor water solubility and low bioavailability. This review summarizes the current studies of the structural diversity of antitumor BA derivatives within the last five years, which provides prospects for further research on the structural modification of betulinic acid. [Display omitted] [ABSTRACT FROM AUTHOR]

In this study, we designed a novel nucleus-targeted nanocarrier (NLS-KALA-SA, NKSN) consisting of Kala peptide (KALA), nuclear localization signal (NLS) and stearic acid (SA) using Fmoc solid phase synthesis method. We chose Curcumin (CUR), Paclitaxel (PTX), Ginsenoside compound K(CK) as models of poorly water-soluble antitumor drugs, The drugs loaded NLS-KALA-SA nanoparticles (CUR/NKSN, PTX/NKSN, CK/NKSN) were obained by the dialysis method, their physicochemical properties were determined and antitumor activity were evaluated. The NLS-KALA-SA nanoparticles were spherical shaped with an average size of 76.4 ± 7.6 mm and a zeta potential of 43.7 ± 5.8 mV. The drug-loaded NLS-KALA-SA nanoparticles were above 86.1% and 17.1% in entrapment efficiency and drug loading capacity, and had sustained drug release behavior. Biodistribution and cellular uptake study exhibited that PTX/NKSN mainly distributed in tumor site of A549-bearing mice, and coumarin-6(C6) loaded NLS-KALA-SA nanoparticle (C6/NKSN) was predominantly accumulated in the nucleus of A549 cells. Western blot analysis indicated that PTX/NKSN could more remarkably inhibit Bcl-2 expression and enhance the expression of Bax and Caspase-3 as compared to the controls in A549 cells. Cell apoptosis and antitumor activity study showed that PXT/NKSN could more obviously induce apoptosis of A549 cells compared with free PXT, the PTX/NKSN administration was more effective than free PTX for lung cancer treatment and displayed mild toxicity in A549-bearing mice. The results demonstrates that the NLS-KALA-SA nanoparticles system could enhance the antitumor effects of the encapsulated drug and reduce tissue toxicity due to its long circulating properties and tumor targeting, which might provide a promising strategy for lung cancer treatment. [ABSTRACT FROM AUTHOR]

The delivery of therapeutics into sites of action by using cargo-delivery platforms potentially minimizes their premature degradation and fast clearance from the bloodstream. Additionally, drug-loaded stimuli-responsive supramolecular assemblies can be produced to respond to the inherent features of tumor microenvironments, such as extracellular acidosis. We report in this framework the use of pH-responsive polymersomes (PSs) manufactured using poly([ N -(2-hydroxypropyl)] methacrylamide) 35 - b -poly[2-(diisopropylamino)ethyl methacrylate] 75 as the building unit (PHPMA 35 - b -PDPA 75). The self-assemblies were produced with desired size towards long circulation time and tumor accumulation (hydrodynamic diameter - D H ~ 100 nm), and they could be successfully loaded with 10% w / w DOX (doxorubicin), while maintaining colloidal stability. The DOX loaded amount is presumably mainly burst-released at the acidic microenvironment of tumors thanks to the pH-switchable property of PDPA (pKa ~ 6.8), while reduced drug leakage has been monitored in pH 7.4. Compared to the administration of free DOX, the drug-loaded supramolecular structures greatly enhanced the therapeutic efficacy with effective growth inhibition of EL4 lymphoma tumor model and 100% survival rate in female C57BL/6 black mice over 40 days. The approach also led to reduced cardiotoxic effect. These features highlight the potential application of such nanotechnology-based treatment in a variety of cancer therapies where low local pH is commonly found, and emphasize PHPMA-based nanomedicines as an alternative to PEGylated formulations. [Display omitted] [ABSTRACT FROM AUTHOR]

Drug repurposing is a promising strategy for identifying new applications for approved drugs. Here, we describe a polymer biomaterial composed of the antiretroviral drug ritonavir derivative (5-methyl-4-oxohexanoic acid ritonavir ester; RD), covalently bound to HPMA copolymer carrier via a pH-sensitive hydrazone bond (P-RD). Apart from being more potent inhibitor of P-glycoprotein in comparison to ritonavir, we found RD to have considerable cytostatic activity in six mice (IC 50 ~ 2.3–17.4 μM) and six human (IC 50 ~ 4.3–8.7 μM) cancer cell lines, and that RD inhibits the migration and invasiveness of cancer cells in vitro. Importantly, RD inhibits STAT3 phosphorylation in CT26 cells in vitro and in vivo , and expression of the NF-κB p65 subunit, Bcl-2 and Mcl-1 in vitro. RD also dampens chymotrypsin-like and trypsin-like proteasome activity and induces ER stress as documented by induction of PERK phosphorylation and expression of ATF4 and CHOP. P-RD nanomedicine showed powerful antitumor activity in CT26 and B16F10 tumor-bearing mice, which, moreover, synergized with IL-2-based immunotherapy. P-RD proved very promising therapeutic activity also in human FaDu xenografts and negligible toxicity predetermining these nanomedicines as side-effect free nanosystem. The therapeutic potential could be highly increased using the fine-tuned combination with other drugs, i.e. doxorubicin, attached to the same polymer system. Finally, we summarize that described polymer nanomedicines fulfilled all the requirements as potential candidates for deep preclinical investigation. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] Hyaluronic acid (HA) possesses unique biological properties that bring many biomedical applications. Nanocomposite of HA has the potential to release the drug at the overexpression of CD44 receptor for tumor growth inhibition. Properties of HA and different forms of CD44 receptor with their effect in drug delivery have discussed in this article. This article briefly discusses preparation, purification, characterization and commercial production of HA derivatives. Number of preparation methods of HA nanocomposites with their advantages and disadvantages and similarities and dissimilarities among them also included broadly in this article. Various HA nanoforms like HA nanogels, HA nanoparticles, carbon based HA nanostructures and HA nano-fibers also added to give the elaborated dimensions to the readers. Most importantly the inclusion of HA based nanocomposites as drug delivery vehicle for tumor treatment will give the future course of research plan for the researchers. The whole manuscript majorly focuses on the role of HA in its anti-tumor activity. [ABSTRACT FROM AUTHOR]