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A nitric oxide (NO) photodonor (1) capable of releasing two NO molecules through a stepwise mechanism has been covalently grafted to blue-emitting N-doped carbon dots (NCDs). The resulting water-soluble nanoconjugate (NCDs-1), ca. 10 nm in diameter, exhibits a new absorption band not present in the simple physical mixture of the two components and is attributable to strong electronic interactions between them in the ground state. Blue light excitation of NCDs-1 leads to NO photogeneration with an efficiency almost one order of magnitude higher than that observed for 1 alone, probably due to a photoinduced electron transfer between the NCDs and the grafted 1. Photoexcitation of the nanoconjugate also results in effective photothermal conversion, which is negligible in the naked NCDs. Furthermore, in contrast to 1, the nanoconjugate liberates NO also under excitation with green light. Finally, the typical blue fluorescence of the NCDs is quenched in NCDs-1 but restored upon the photouncaging of the second NO molecule, providing readable and real-time information about the amount of NO photogenerated.

Triple-negative breast cancer (TNBC) is recognized as a major aggressive subtype of breast cancer due to its expeditious worsening growth, extensive metastatic capability, and recalcitrance to standard current treatments. Hesperetin (HSP), a natural bioflavonoid from citrus fruits, demonstrates pronounced anticancer efficacy, but its hydrophobicity limits its clinical development. The present study reports the fabrication of a biocompatible and pH-responsive transferrin (TF) receptor-targeted HSP-loaded poly(lactic- co -glycolic acid) (PLGA) nanobioconjugate (PLGA-HSP-TF NPs) and the exploration of its in vitro and in vivo antineoplastic potential. PLGA nanoparticles (NPs), PLGA-HSP NPs, and PLGA-HSP-TF NPs were synthesized and characterized by DLS, FTIR, FE-SEM, and 1 H NMR spectroscopy. The stability and in vitro release profile of nanoparticles were inspected, and anticancer efficacy was scrutinized in terms of in vitro cytotoxicity, oxidative stress and apoptosis biomarkers, and cell cycle arrest. In vivo tumor regression and host survival studies were executed in Ehrlich ascites carcinoma (EAC) cell-bearing Swiss albino mice. The drug uptake of highly stable PLGA-HSP-TF NPs was accomplished effectively in MDA-MB-231 cells and showed the pH-dependent intracellular release of HSP, which generated excessive intracellular reactive oxygen species (ROS) that led to oxidative assault to the TNBC cells. This elevated ROS dropped the mitochondrial membrane potential and triggered apoptosis-mediated cell death by arresting the cell cycle at the G0/G1 phase. Furthermore, PLGA-HSP-TF NPs unveiled significant in vivo Ehrlich ascites carcinoma regression and host survival compared to free HSP with minimum toxicity at a minimum dose of 20 mg/kg body weight. The study divulges that PLGA-HSP-TF NPs may be an astounding anticancer nanocandidate for aggressive triple-negative breast cancer therapy.

Hypocrellin-based photodynamic therapy (PDT) is developing as a viable cancer therapeutic option, especially when enhanced by nanoconjugation. This review investigates the methods by which nano-conjugated hypocrellin enhances therapeutic efficacy and precision when targeting cancer cells. These nanoconjugates encapsulate or covalently bind hypocrellin photosensitizers (PSs), allowing them to accumulate preferentially in malignancies. When activated by light, the nanoconjugates produce singlet oxygen and other reactive oxygen species (ROS), resulting in oxidative stress that selectively destroys cancer cells while protecting healthy tissues. We look at how they can be used to treat a variety of cancers. Clinical and preclinical studies show that they have advantages such as increased water solubility, improved tumor penetration, longer circulation times, and tailored delivery, all of which contribute to fewer off-target effects and overall toxicity. Ongoing research focuses on improving these nanoconjugates for better tumor targeting, drug release kinetics, and overcoming biological obstacles. Furthermore, the incorporation of developing technologies such as stimuli-responsive nanocarriers and combination therapies opens exciting opportunities for enhancing hypocrellin-based PDT. In conclusion, the combination of hypocrellin and nanotechnology constitutes a significant approach to cancer treatment, increasing the efficacy and safety of PDT. Future research will seek to create conjugates including hypocrellin, herceptin, and gold nanoparticles to induce apoptosis in human breast cancer cells in vitro, opening possibilities for therapeutic applications., Competing Interests: There are no disclosed conflicts of interest by the authors of this study., (© 2024 Rajan et al.)

Managing advanced colon cancer is challenging, requiring targeted therapies. This study presents a novel nanoconjugate system, HA-CMD@ETP-MLT-NCs, designed to deliver etoposide (ETP) specifically to colon cancer cells. The system consists of Hyaluronic Acid (HA)-Functionalized Carboxymethyl Dextran (CMD) coated with Melatonin (MLT). The nanoconjugates showed good stability, with a zeta potential of -29.90 mV and a particle size of 199.1 nm. They achieved an 80.3 % yield and a high drug entrapment efficiency of 93.4 %. In vitro release studies demonstrated pH-dependent drug release, with 73.4 % released at pH 5.5 (tumour-like environment) and 42.6 % at pH 7.4 (normal tissue) over 24 h. The nanoconjugates improved cellular uptake, induced apoptosis, and reduced reactive oxygen species (ROS) in HCT116 colon cancer cells. Flow cytometry showed a significant decrease in ROS levels, and lipid peroxidation inhibition increased to 56.67 %. These findings suggest that HA-CMD@ETP-MLT-NCs enhance etoposide delivery and reduce side effects. Further in vivo studies and clinical trials are needed to confirm its therapeutic potential., Competing Interests: Declaration of competing interest Authors declare there are no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ovarian cancer is the deadliest gynecological malignancy, representing 2.5 % of all female cancers and accounting for 5 % of female cancer-related fatalities. Despite numerous strategies in its treatment, the disease shows a high recurrence rate and a low survival rate. Consequently, there is a growing focus on targeted therapies in ovarian cancer treatment. It is well-known that VEGFR and LPA pathways undergo alterations in ovarian cancer and stimulate survival, adhesion, migration, invasion, tumor growth and angiogenesis. Cabozantinib (CBZ) is a multi-receptor tyrosine kinase inhibitor that effectively targets MET, VEGFR-1, 2, 3, FLT3, c-KIT, and RET. Ki16425 is a selective inhibitor of LPA receptors 1, 2, and 3. Therefore, targeting LPA receptors and combining with VEGFR inhibitor is a strategic approach for ovarian cancer treatment. In this study, it was aimed to prepare polymer-drug nanoconjugate for both VEGFR and LPAR inhibition. For this, O-(2-Carboxyethyl) polyethylene glycol (PEG 5000 ) which advantages are known in cancer studies, was chosen as the carrier system, and a nanoconjugate containing Ki16425 and CBZ (Ki-PEG-CBZ) was synthesized and its potential was evaluated. Initially, CBZ and Ki16425 were conjugated to the PEG 5000 through pH-sensitive hydrazone and ester bonds. After nanoconjugate characterization, in vitro release and its ovarian cancer treatment potential were evaluated on A2780, OVCAR3 and SKOV3 ovarian cancer cell lines. A nanoconjugate was obtained with a particle size of 169 ± 15.23 nm, a zeta potential of -13.5 ± 1.21 mV, and a release profile lasting 48 h, containing CBZ and Ki16425 with drug loading efficiencies of 73.71 ± 0.53 % and 77.72 ± 2.51 %, respectively. In vitro studies have demonstrated that Ki-PEG-CBZ is highly effective against ovarian cancer. We suggest that the developed polymer-drug nanoconjugate is an effective and safe nanoconjugate for the treatment of ovarian cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this study, we report the synthesis and characterization of pH-responsive nanoconjugates for targeted drug delivery. Galactomannan extracted from D. regia seeds was oxidized to form aldehyde groups, achieving a percentage of oxidation of 25.6 %. The resulting oxidized galactomannan (GMOX) was then copolymerized with PINIPAm-NH 2 , yielding a copolymer. The copolymer exhibited signals from both GMOX and PNIPAm-NH 2 in its NMR spectrum, confirming successful copolymerization. Critical association concentration (CAC) studies revealed the formation of nanostructures, with lower CAC values observed at higher temperatures. The copolymer and GMOX reacted with doxorubicin (DOX), resulting in nanoconjugates with controlled drug release profiles, especially under acidic conditions similar to tumor microenvironments. Cytotoxicity assays demonstrated significant efficacy of the nanoconjugates against melanoma cells with reduced toxicity towards healthy cells. These findings underscore the potential of the pH-responsive nanoconjugates as promising candidates for targeted cancer therapy, offering improved therapeutic efficacy and reduced systemic side effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could appear to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Docetaxel (DTX) has become widely accepted as a first-line treatment for metastatic breast cancer; however, the frequent development of resistance provides challenges in treating the disease.C 60 fullerene introduces a unique molecular form of carbon, exhibiting attractive chemical and physical properties. Our study aimed to develop dicarboxylic acid-derivatized C 60 fullerenes as a novel DTX delivery carrier. This study investigated the potential of water-soluble fullerenes to deliver the anti-cancer drug DTX through a hydrophilic linker. The synthesis was carried out using the Prato reaction. The spectroscopic analysis confirmed the successful conjugation of DTX molecules over fullerenes. The particle size of nanoconjugate was reported to be 122.13 ± 1.63 nm with a conjugation efficiency of 76.7 ± 0.14%. The designed conjugate offers pH-dependent release with significantly less plasma pH, ensuring maximum release at the target site. In-vitro cell viability studies demonstrated the enhanced cytotoxic nature of the developed nanoconjugate compared to DTX. These synthesized nanoscaffolds were highly compatible with erythrocytes, indicating the safer intravenous route administration. Pharmacokinetic studies confirmed the higher bioavailability (~ 6 times) and decreased drug clearance from the system vis-à-vis plain drug. The histological studies reveal that nanoconjugate-treated tumour cells exhibit similar morphology to normal cells. Therefore, it was concluded that this developed formulation would be a valuable option for clinical use., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

The basis of most neurological syndromes is the accumulation of free radical molecules. Quercetin is a polyphenolic bioflavonoid molecule and it has a very strong antioxidant effect by maintaining oxidative balance. There are many difficulties in the clinical use of quercetin due to its hydrophobic structure, low solubility, instability, poor oral bioavailability, and limited tissue-barrier penetration. Its synergistic use in complex with gold nanoparticles (AuNPs) could overcome these problems. AuNPs have recently emerged as an attractive candidate for delivery applications of various biomolecules and drugs. The aim of this study was to synthesize two different sized gold nanoparticles (AuNP 20 and AuNP 50 ) modified with polyethyleneimine (PEI) and quercetin, evaluate their potential neuroprotective effects on the in vitro oxidative stress model using DRG primary sensory neurons. It was shown that the antioxidant and anti-apoptotic ability of the bioflavonoid was preserved after exposure to the designed quercetin modified AuNPs. The PEI surface coating increased the stability and biocompatibility of the AuNPs in both sizes. It also potentially enables additional surface functionalization. This study indicates that designed nanoparticles (AuNP-Q-PEI) with different sizes could be a useful potential platform for the treatment of neurodegenerative syndromes or cancer diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Background: Antimicrobial resistance has emerged as a major global health threat, necessitating the urgent development of new antimicrobials through innovative methods to combat the rising prevalence of resistant microbes. With this view, we developed three novel nanoconjugates using microbial natural pigment for effective application against certain pathogenic microbes., Results: A natural red pigment (RP) extracted from the endophyte Monascus ruber and gamma rays were applied to synthesize RP-ZnO, RP-CuO, and RP-MgO nanoconjugates. The synthesized nanoconjugates were characterized by different techniques to study their properties. The antimicrobial potential of these nanoconjugates was evaluated. Moreover, the antibiofilm, protein leakage, growth curve, and UV light irradiation effect of the synthesized nanoconjugates were also studied. Our results confirmed the nano-size, shape, and stability of the prepared conjugates. RP-ZnO, RP-CuO, and RP-MgO nanoconjugates showed broad antimicrobial potential against the tested bacterial and fungal pathogens. Furthermore, the RP-ZnO nanoconjugate possessed the highest activity, followed by the RP-CuO against the tested microbes. The highest % inhibition of biofilm formation by the RP-ZnO nanoconjugate. Membrane leakage of E. coli and S. aureus by RP-ZnO nanoconjugate was more effective than RP-MgO and RP-CuO nanoconjugates. Finally, UV light irradiation intensified the antibiotic action of the three nanoconjugates and RP-ZnO potential was greater than that of the RP-MgO, and RP-CuO nanoconjugates., Conclusion: These findings pave the way for exploiting the synthesized nanoconjugates as potential materials in biomedical applications, promoting natural, green, and eco-friendly approaches., (© 2024. The Author(s).)

Leishmaniasis, attributed to the protozoan parasite Leishmania , manifests in diverse clinical forms, including cutaneous, mucocutaneous, and visceral leishmaniasis; VL constitutes a significant global health menace. Prevalent in tropical and subtropical regions, this affliction disproportionately impacts individuals below the poverty threshold, transmitted through the bite of female sandflies. Existing treatments, such as pentavalent antimony, miltefosine, and Amphotericin B, exhibit limitations. Despite the emergence of liposomal Amphotericin B (AmBisome) as a promising antileishmanial agent, its utility is impeded by adverse effects, elevated production expenses, and cytotoxicity. To address these challenges, our investigation introduces a potential remedy─a citrate-coated gold Amphotericin B nanoparticle formulation. Characterized using dynamic light scattering and transmission electron microscopy, this pioneering formulation exhibited efficacy against L. donovani Ag83 promastigotes as demonstrated by MTT cell viability testing. Evaluating internal reactive oxygen species (ROS) levels and dual staining with acridine orange and ethidium bromide unveiled its consequential impact on cell death. Significantly, our study discloses this novel nanoformulation's unprecedented inhibition of the trypanothione reductase enzyme. The findings posit the citrate-coated gold Amphotericin B nanoformulation as a promising and targeted antileishmanial agent, representing potential advancements in leishmaniasis therapeutics.

The anticancer efficacy of doxorubicin, an anthracycline-based and FDA-approved chemotherapeutic drug, is significantly hindered by acquired chemoresistance and severe side effects despite its potent anticancer properties. To overcome these challenges, we developed an innovative therapeutic formulation that integrates targeted chemotherapy and phototherapy within a single platform using gold nanoparticles (AuNPs). This novel nanoconjugate, designated as Dox-Fe@FA-AuNPs, is co-functionalized with folic acid, doxorubicin, and an iron(III)-phenolate/carboxylate complex, enabling cancer-specific drug activation. Here, we report the synthesis, characterization, and comprehensive physico-chemical and biological evaluations of Dox-Fe@FA-AuNPs. The nanoconjugate exhibited excellent solubility, stability, and enhanced cellular uptake in folate receptor-positive cancer cells. The nanoconjugate was potently cytotoxic against HeLa and MDA-MB-231 cancer cells (HeLa: 105.5±16.52 μg mL -1 ; MDA-MB-231: 112.0±12.31 μg mL -1 ; MDA-MB-231 (3D): 156.31±19.35 μg mL -1 ) while less cytotoxic to the folate(-) cancer cells (MCF-7, A549 and HepG2). The cytotoxicity was attributed to the pH-dependent release of doxorubicin, which preferentially occurs in the acidic tumor microenvironment. Additionally, under red light irradiation, the nanoconjugate generated ROS, inducing caspase-3/7-dependent apoptosis with a photo-index (PI) >50, and inhibited cancer cell migration. Our findings underscore the potential of Dox-Fe@FA-AuNPs as a highly effective and sustainable platform for targeted chemo-phototherapy., (© 2024 Wiley-VCH GmbH.)

Nanotechnology-based cancer treatment has received considerable attention, and these treatments generally use drug-loaded nanoparticles (NPs) to target and destroy cancer cells. Nanotechnology combined with photodynamic therapy (PDT) has demonstrated positive outcomes in cancer therapy. Combining nanotechnology and PDT is effective in targeting metastatic cancer cells. Nanotechnology can also increase the effectiveness of PDT by targeting cells at a molecular level. Dendrimer-based nanoconjugates (DBNs) are highly stable and biocompatible, making them suitable for drug delivery applications. Moreover, the hyperbranched structures in DBNs have the capacity to load hydrophobic compounds, such as photosensitizers (PSs) and chemotherapy drugs, and deliver them efficiently to tumour cells. This review primarily focuses on DBNs and their potential applications in cancer treatment. We discuss the chemical design, mechanism of action, and targeting efficiency of DBNs in tumour metastasis, intracellular trafficking in cancer treatment, and DBNs' biocompatibility, biodegradability and clearance properties. Overall, this study will provide the most recent insights into the application of DBNs and PDT in cancer therapy.

Recently, gold nanoparticles (Au Nps) have gained tremendous attention for its unique properties as a safe nanocarrier for delivering drugs that are used in different disease diagnoses. Although silver nanoparticles (Ag NPs) have been generally applied due to their strong antibacterial, antiviral, antifungal, and antimicrobial properties, their toxicity is a subject of sustained debate, thus requiring further studies. The present study aims to evaluate the potential protective effect of gold nanoparticles and phthalocyanine-gold nanoconjugates (Pc-Au NCs) against the hepatorenal toxicity of silver nanoparticles in male rats. Herein, 60 adult male Rattus norvegicus rats were divided into six equal groups (n = 10/group); the first group was kept as control, the second received gold nanoparticles (Au NPs) intraperitoneally (10 µg/kg) daily for 3 weeks, the third group is gold-phthalocyanine (Pc-Au) group where rats were injected intraperitoneally with gold-phthalocyanine for 3 weeks (10 µg/kg), the fourth group received silver nanoparticles (Ag NPs) (4 mg/kg) daily intraperitoneally for 3 weeks, the fifth group is silver + gold nanoparticles group (Ag + Au), and the sixth is silver + gold-phthalocyanine nanoconjugates (Ag + Pc-Au) group in which rats were intraperitoneally injected firstly with Ag NPs (4 mg/kg) for 3 weeks then with gold or gold-phthalocyanine for another 3 weeks (10 µg/kg). Our results revealed that Ag NPs could increase the serum AST, ALT, ALP, urea, creatinine, and lipid profile and significantly decreased the total protein and albumin. Moreover, histopathological alterations detected in the kidney and the liver of the Ag NPs group included vascular congestion, inflammatory cell infiltration, and tissue distortion. Alongside, exposure to Ag NPs induces hepatic and renal oxidative stress by suppressing the antioxidant-related genes including glutathione peroxidase 1 (gpx1), superoxide dismutase (sod), and catalase (cat). Ag NPs also upregulated the hepatic and renal genes involved in inflammation such as the interleukin-6 (il-6) and tumor necrosis factor-α (tnf-α), nuclear factor kappa B (nf-κβ), apoptosis such as the BCL2 associated X (bax), casp3, and other related to metabolism including asparagine synthetase (asns), suppressor of cytokine signaling 3 (socs3), MYC proto-oncogene (myc), and C-C motif chemokine ligand 2 (ccl2). On the other hand, treatment with Au NPs and Pc-Au NCs could effectively ameliorate the hepatorenal damages induced by Ag NPs and improve liver and kidney architecture and function, especially in the Pc-Au NCs group. Briefly, our study revealed the underlined mechanism of Ag NPs hepatotoxic and nephrotoxic effects and that Pc-Au NCs could alleviate these adverse impacts via their anti-oxidative, anti-apoptotic, and anti-inflammatory activities., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Metformin, the primary therapy for type 2 diabetes mellitus (T2DM), showed limitations such as varying absorption, rapid system clearance, required large amount, resistance, longstanding side effects. Use of Nano formulations for pharmaceuticals is emerging as a viable technique to reduce negative consequences of drug, while simultaneously attaining precise release and targeted distribution. This study developed a Polyethylene Glycol conjugated Graphene Oxide Quantum dots (GOQD-PEG) nanocomposite for the sustained release of metformin. Herein, we evaluated the effectiveness of metformin-loaded nanoconjugate in in vitro insulin resistance model. Results demonstrated drug loaded nanoconjugate successfully restored glucose uptake and reversed insulin resistance in in vitro conditions at reduced dosage compared to free metformin., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sarkar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Bacteriocins are antimicrobial peptides produced by bacteria to prevent the growth of pathogens. Combining bacteriocins with metal nanoparticles, like silver nanoparticles (AgNPs), has developed into a viable strategy to get over bacteriocin limitations. In this study, bacteriocin BacZY05 was extracted from Bacillus subtilis ZY05 and purified using various techniques. The resulting purified bacteriocin was then combined with silver nanoparticles to form bacteriocin silver nanoconjugates (BacZY05-AgNPs). The physicochemical properties of the BacZY05-AgNPs were characterized using various analytical techniques. The mean diameter of the synthesized AgNPs was approximately 20-60 nm with an oval or spherical shape. The antimicrobial activity of the BacZY05-AgNPs was evaluated against several indicator strains by their zone of inhibition (ZOI), using the agar well diffusion method. Compared to bacteriocin (ZOI- 13 to 20 mm) and AgNPs (ZOI- 10-22 mm) alone, the antibacterial activity data demonstrated a 1.3-1.5-fold increase in the activity of bacteriocin-nanoconjugates (ZOI- 22 to 26 mm). For Staphylococcus aureus MTCC3103 and Klebsiella pneumoniae MTCC109, BacZY05-capped AgNPs exhibited the lowest minimum inhibitory concentration (MIC), measuring 10.93 µg/mL. For Salmonella typhi NCIM2501, the MIC was 28.75 µg/mL. The highest MIC value was 57.5 µg/mL for Escherichia coli DH5α and Vibrio cholerae MTCC3909. With BacZY05-capped AgNPs, the lowest minimum bactericidal concentration (MBC) of 28.75 µg/mL was observed for Staphylococcus aureus MTCC31003. In the cases of Salmonella typhi NCIM2501 and Klebsiella pneumoniae MTCC109 concentration was 57.5 µg/mL. Vibrio cholerae MTCC3909 and Escherichia coli DH5α had the highest MBC values at 115 µg/mL., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

To improve the therapeutic activity of inhaled glucocorticoids and reduce potential side effects, we designed a formulation combining the advantages of nanoparticles, which have an enhanced uptake by alveolar cells, allow targeted delivery and sustained drug release, as well as limited drug systemic passage, with those of microparticles, which display good alveolar deposition. Herein, a polymer-drug conjugate, poly(malic acid)-budesonide (PMAB), was first synthesized with either 11, 20, 33, or 43 mol% budesonide (drug:polymer from 1:8 to 3:4), the drug creating hydrophobic domains. The obtained conjugates self-assemble into nanoconjugates in water, yielding excellent drug loading of up to 73 wt%, with 80-100 nm diameters. In vitro assays showed that budesonide could be steadily released from the nanoconjugates, and the anti-inflammatory activity was preserved, as evidenced by reduced cytokine production in LPS-activated RAW 264.7 macrophages. Nanoconjugates were then embedded into microparticles through spray-drying with L-leucine, forming nano-embedded microparticles (NEMs). NEMs were produced with an aerodynamic diameter close to 1 µm and a density below 0.1 g.cm -3 , indicative of a high alveolar deposition. NEMs spray-dried with the less hydrophobic nanoconjugates, PMAB 1:4, were readily dissolved in simulated lung fluid and were chosen for in vivo experiments to study pharmacokinetics in healthy rats. As it was released in vivo from NEMs, sustained distribution of budesonide was obtained for 48 h in lung tissue, cells, and lining fluid. With high loading rates, modulable release kinetics, and low cytotoxicity, these nanoconjugates delivered by NEMs are promising for the more efficient treatment of pulmonary inflammatory diseases., (© 2024. Controlled Release Society.)

In vitro alternative therapy of human epidermoid squamous carcinoma (A431) by superparamagnetic hyperthermia (SPMHT) using Fe 3 O 4 (magnetite) superparamagnetic nanoparticles (SPIONs) with an average diameter of 15.8 nm, bioconjugated with hydroxypropyl gamma-cyclodextrins (HP-γ-CDs) by means of polyacrylic acid (PAA) biopolymer, is presented in this paper. The therapy was carried out at a temperature of 43 °C for 30 min using the concentrations of Fe 3 O 4 ferrimagnetic nanoparticles from nanobioconjugates of 1, 5, and 10 mg/mL nanoparticles in cell suspension, which were previously found by us to be non-toxic for healthy cells (cell viabilities close to 100%), according to ISO standards (cell viability must be greater than 70%). The temperature for the in vitro therapy was obtained by the safe application (without exceeding the biological limit and cellular damage) of an alternating magnetic field with a frequency of 312.4 kHz and amplitudes of 168, 208, and 370 G, depending on the concentration of the magnetic nanoparticles. The optimal concentration of magnetic nanoparticles in suspension was found experimentally. The results obtained after the treatment show its high effectiveness in destroying the A431 tumor cells, up to 83%, with the possibility of increasing even more, which demonstrates the viability of the SPMHT method with Fe 3 O 4 -PAA-(HP-γ-CDs) nanobioconjugates for human squamous cancer therapy., Competing Interests: The authors declare no conflicts of interest.

The tumor immunosuppressive microenvironment (TIME) and uncontrollable release of antigens can lower the efficacy of nanovaccine-based immunotherapy (NBI). Therefore, it is necessary to develop a new strategy for TIME reshaping and controllable release of antigens to improve the NBI efficacy. Herein, an acidity-responsive Schiff base-conjugated polyphenol-coordinated nanovaccine was constructed for the first time to realize bidirectional TIME reshaping and controllable release of antigens for activating T cells. In particular, an acidity-responsive tannic acid-ovalbumin (TA-OVA) nanoconjugate was prepared via a Schiff base reaction. Fe III was coordinated with TA-OVA to produce a Fe III -TA-OVA nanosystem, and 1-methyltryptophan (1-MT) as an indoleamine 2,3-dioxygenase inhibitor was loaded to form a polyphenol-coordinated nanovaccine. The coordination between Fe III and TA could cause photothermal ablation of primary tumors, and the acidity-triggered Schiff base dissociation of TA-OVA could controllably release OVA to realize lysosome escape, initiating the body's immune response. More importantly, oxidative stress generated by a tumor-specific Fenton reaction of Fe ions could promote the polarization of tumor-associated macrophages from the M2 to M1 phenotype, resulting in the upregulation of cytotoxic T cells and helper T cells. Meanwhile, 1-MT could downregulate immunosuppressive regulatory T cells. Overall, such skillful combination of bidirectional TIME reshaping and controllable antigen release into one coordination nanosystem could effectively enhance the NBI efficacy of tumors.

Novel amphiphilic nanoconjugates of hyaluronic acid (HA), 50 kDa (HA 50 ) and 100 kDa (HA 100 ), and the lipopeptide biosurfactant surfactin (SF) were developed for potential anticancer applications. Physicochemical characterization indicated the formation of an ester conjugate (HA: SF molar ratio 1: 40) with the HA 50 -SF derivative exhibiting higher degree of substitution, hydrolytic stability, and surface activity. Self-assembly resulted in nanomicelles with smaller size and greater negative charge relative to SF micelles. Biological data demonstrated distinct anticancer activity of HA 50 -SF which displayed greater synergistic cytotoxicity and selectivity for MDA-MB 231 and MCF-7 breast cancer cells alongside greater modulation of apoptosis-related biomarkers leading to apoptosis. As bioactive vector for chemotherapeutic agents, the selected HA 50 -SF nanoconjugate efficiently (70 %) entrapped berberine (BER) producing a sustained release BER-HA 50 -SF synergistic anticancer nanoformulation. Lactoferrin (Lf) coating for dual HA/Lf targeting endowed Lf/BER-HA 50 -SF with significantly greater selectivity for both cell lines. A murine Ehrlich breast cancer model provided evidence for the efficacy and safety of Lf/BER-HA 50 -SF via tumoral, histological, immunohistochemical, molecular and systemic toxicity assessments. Thus, HA-SF nanoconjugates integrating the HA and SF properties and biofunctionalties present a novel biopolymer-biosurfactant platform of benefit to oncology nanomedicine and possibly other applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Novel strategies for treating triple-negative breast cancer (TNBC) are ongoing because of the lack of standard-of-care treatment. Nanoframed materials with a protein pillar are considered a valuable tool for designing multigoals of energy-absorbing/medication cargo and are a bridge to cross-conventional treatment strategies., Methods: Nanobioconjugates of gold nanoclusters-bovine serum albumin (AuNCs-BSA) and doxorubicin-AuNCs-BSA (Dox-AuNCs-BSA) were prepared and employed as a simultaneous double photosensitizer/sonosensitizer and triple chemotherapeutic/photosensitizer/sonosensitizer, respectively., Results: The highly stable AuNCs-BSA and Dox-AuNCs-BSA have ζ potentials of -29 and -18 mV, respectively, and represent valuable photothermal and sonodynamic activities for the combination of photothermal therapy and sonodynamic therapy (PTT/SDT) and synchronized chemotherapy/photothermal therapy/sonodynamic therapy (CTX/PTT/SDT) of human TNBC cells, respectively. The efficiency of photothermal conversion of AuNCs-BSA was calculated to be a promising value of 32.9%. AuNCs-BSA and Dox-AuNCs-BSA were activated on either laser light irradiation or ultrasound exposure with the highest efficiency on the combination of both types of radiation. CTX/PTT/SDT of MCF-7 and MDA-MB-231 breast cancer cell lines by Dox-AuNCs-BSA were evaluated with the MTT cell proliferation assay and found to progress synergistically., Conclusion: Results of the MTT assay, detection of the generation of intracellular reactive oxygen species and occurrence of apoptosis in the cells confirmed that CTX/PTT/SDT by Dox-AuNCs-BSA was attained with lower needed doses of the drug and improved tumor cell ablation, which would result in the enhancement of therapeutic efficacy and overcoming of therapeutic resistance., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2024 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

The search for effective production of xylanase which is an important industrial enzyme led to the present study that explored xylanase production by Aspergillus sydowii SF through Taguchi optimization that incorporated nanoconjugates in submerged fermentation. Calcium and zinc oxide nanoconjugates biosynthesized by xylanase were characterized via UV-Vis spectroscopy, Fourier transform infrared spectroscopy, and Transmission electron microscopy (TEM). The xylanase-mediated calcium oxide and zinc oxide nanoconjugates with λ max of 374 and 316 nm, respectively, and were 5.32-17.69 nm in size. Xylanase production was improved by 2.90-10.58 folds (64.24-234.15 U/mL) through Taguchi optimization cum nanoconjugates, and ANOVA showed that nanoconjugates contributed 13.62-65.97% to improved production. The xylanase had up to 88.38% deinking activity, with 49.60-84.64% removal of blue color. The remarkable xylanase production, its use to biosynthesize nanoconjugates and biodeinking potentials contribute to the development of versatile biocatalysts with applications in biotechnology, nanotechnology, and sustainable paper production. To the best of our knowledge, this represents the first report of xylanase for biosynthesis of calcium oxide and zinc oxide nanoparticles, as well as nanosupplementation to induce xylanase production, which can open new vista in bioprocess optimization.

The combination of immunotherapy and chemotherapy to ablate tumors has attracted substantial attention due to the ability to simultaneously elicit antitumor immune responses and trigger direct tumor cell death. However, conventional combinational strategies mainly focus on the employment of drug carriers to deliver immunomodulators, chemotherapeutics, or their combinations, always suffering from complicated preparation and carrier-relevant side effects. Here, the fabrication of bacterial flagellum-drug nanoconjugates (FDNCs) for carrier-free immunochemotherapy is described. FDNCs are simply prepared by attaching chemotherapeutics to amine residues of flagellin through an acid-sensitive and traceless cis-aconityl linker. By virtue of native nanofibrous structure and immunogenicity, bacterial flagella not only show long-term tumor retention and highly efficient cell internalization, but also provoke robust systemic antitumor immune responses. Meanwhile, conjugated chemotherapeutics exhibit an acid-mediated release profile and durable intratumoral exposure, which can induce potent tumor cell inhibition via direct killing. More importantly, this combination is able to augment immunoactivation effects associated with chemotherapy-enabled immunogenic tumor cell death to further enhance antitumor efficacy. By leveraging the innate response of the immune system to pathogens, the conjugation of therapeutic agents with self-adjuvant bacterial flagella provides an alternative approach to develop carrier-free nanotherapeutics for tumor immunochemotherapy., (© 2023 Wiley-VCH GmbH.)

Antimicrobial photodynamic therapy (APDT) utilizes photosensitizers (PSs) that eradicate a broad spectrum of bacteria in the presence of light and molecular oxygen. On the other hand, some light sources such as ultraviolet (UVB and UVC) have poor penetration and high cytotoxicity, leading to undesired PDT of the PSs. Herein, we have synthesized conjugatable mesosubstituted porphyrins and extensively characterized them. Time-dependent density functional theory (TD-DFT) calculations revealed that metalloporphyrin EP (5) is a suitable candidate for further applications. Subsequently, the metalloporphyrin was conjugated with lignin-based zinc oxide nanocomposites (ZnOAL and ZnOKL) to develop hydrophilic nanoconjugates (ZnOAL@EP and ZnOKL@EP). Upon dual light (UV + green light) exposure, nanoconjugates showed enhanced singlet oxygen generation ability and also demonstrated pH responsiveness. These nanoconjugates displayed significantly improved APDT efficiency (4-7 fold increase) to treat bacterial infection under dual light irradiation.

Photo-redox chemistry resulting from ligand to metal charge transfer in red-light-activable iron(III) complexes could be a potent strategic tool for next-generation photochemotherapeutic applications. Herein, we developed an iron(III) complex and folate co-functionalized gold nanoconjugate (Fe@FA-AuNPs) and thoroughly characterized it with NMR, ESI MS, UV-visible, EPR, EDX, XPS, powder X-ray diffraction, TEM and DLS studies. There was a remarkable shift in the SPR band of AuNPs to 680 nm, and singlet oxygen ( 1 O 2 ) and hydroxyl radicals were potently generated upon red-light activation, which were probed by UV-visible and EPR spectroscopic assays. Cellular uptake studies of the nanoconjugate (Fe@FA-AuNPs) revealed significantly higher uptake in folate(+) cancer cells (HeLa and MDA-MB-231) than folate(-) (A549) cancer cells or normal cells (HPL1D), indicating the targeting potential of the nanoconjugate. Confocal imaging indicated primarily mitochondrial localization. The IC 50 values of the nanoconjugate determined from a cell viability assay in HeLa, MDA-MB-231, and A549 cells were 27.83, 39.91, and 69.54 μg mL -1 , respectively in red light, while in the dark the values were >200 μg mL -1 ; the photocytotoxicity was correlated with the cellular uptake of the nanoconjugate. The nanocomposite exhibited similar photocytotoxicity (IC 50 in red light, 37.35 ± 8.29 μg mL -1 and IC 50 in the dark, >200 μg mL -1 ). Mechanistic studies revealed that intracellular generation of ROS upon red-light activation led to apoptosis in HeLa cells. Scratch-wound-healing assays indicated the inhibition of the migration of MDA-MB-231 cells treated with the nanoconjugate and upon photo-activation. Overall, the nanoconjugate has emerged as a potent tool for next-generation photo-chemotherapeutics in the clinical arena of targeted cancer therapy.

Aim: A study of the enhancement of photodynamic activities of pyropheophorbide-a using PG-Ag-PPa nanoconjugates. Materials & methods: The nanoconjugates were formulated from silver nanoparticles and PPa via amide linkage, then characterized, and their photodynamic activities were examined. Results: The nanoconjugates displayed a higher rate of reactive oxygen species generation, commendable cellular uptake by Eca-109 cancer cells, higher photocytotoxicity toward the cancer cells and better bio-safety. They revealed strong antibacterial activity against Escherichia coli following internal reactive oxygen species generation and membrane disintegration. The in vivo anticancer studies confirmed higher cytotoxicity of the nanoconjugates toward cancer cells and better safety than PPa. Conclusion : Therefore, PG-Ag-PPa nanoconjugates could be considered potential nano photosensitizers for photodynamic therapy of tumors and bacterial infection with good bio-safety.

Protein-polysaccharide nanoconjugates are covalently interactive networks that are currently the subject of intense research owing to their emerging applications in the food nanotechnology field. Due to their biocompatibility and biodegradability properties, they have played a significant role as wall materials for the formation of various nanostructures to encapsulate nutraceuticals. The food-grade protein-polysaccharide nanoconjugates would be employed to enhance the delivery and stability of nutraceuticals for their real use in the food industry. The most common edible polysaccharides (cellulose, chitosan, pectin, starch, carrageenan, fucoidan, mannan, glucomannan, and arabic gum) and proteins (silk fibroin, collagen, gelatin, soy protein, corn zein, and wheat gluten) have been used as potential building blocks in nano-encapsulation systems because of their excellent physicochemical properties. This article broadens the discussion of food-grade proteins and polysaccharides as nano-encapsulation biomaterials and their fabrication methods, along with a review of the applications of protein-polysaccharide nanoconjugates in the delivery of plant-derived nutraceuticals., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

In this study, a new phthalonitrile derivative namely 4-[(2,4-difluorophenyl)ethynyl]phthalonitrile (1) and its metal phthalocyanines (2 and 3) were synthesized. The resultant compounds were conjugated to silver nanoparticles and characterized using transmission electron microscopy (TEM) images. The biological properties of compounds (1-3), their nanoconjugates (4-6), and silver nanoparticles (7) were examined for the first time in this study. The antioxidant activities of biological candidates (1-7) were studied by applying the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. The highest antioxidant activity was obtained 97.47 % for 200 mg/L manganese phthalocyanine-silver nanoconjugates (6). The antimicrobial and antimicrobial photodynamic therapy (APDT) activities of biological candidates (1-7) were examined using a micro-dilution assay. The highest MIC value was obtained 8 mg/L for nanoconjugate 6 against E. hirae. The studied compounds and their silver nanoconjugates exhibited high APDT activities against all the studied microorganisms. The most effective APDT activities were obtained 4 mg/L for nanoconjugates (5 and 6) against L. pneumophila and E. hirae, respectively. All the studied biological candidates displayed high cell viability inhibition activities against E. coli cell growth. The biofilm inhibition activities of the tested biological candidates were also investigated against S. aureus and P. Aeruginosa. Biological candidates (1-6) can be considered efficient metal nanoparticle-based materials for multi-disciplinary biological applications., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Bacterial polysaccharides can be easily modified to offer dual stimuli-responsive drug delivery systems with double targeting potential. In this research work, bacterial polysaccharides hyaluronic acid (HA) were functionalized with α-tocopherol polyethylene glycol succinate (TPGS) and cholic acid (CA) to form multifunctional polysaccharides nanoconjugates (TPGS-HA-CA). Smart nanoconjugates were synthesized by forming a redox-responsive disulfide bond, and it is composed of double targeting ligands. Doxorubicin (DOX) encapsulated smart nanoconjugates were exhibited an average size of 200 nm with a uniform core-shell structure. It serves the pH-responsive side chain modulation of TPGS-HA-CA, which affords a high degree of swelling at acidic pH. Under the pH 5.0 it shows 57% of release due to the side chain modulation of C-H/N-H. Polysaccharides nanoconjugates exhibited the double stimuli-responsive drug delivery by rapid disassembly of disulfide linkage, which exhibited 72% drug release (pH 5.0+GSH 10 mM). In cytotoxic studies, DOX@TPGS-HA-CA exhibited a higher cytotoxic effect compared to DOX. Hyaluronic acid functionalization with CA, TPGS increases cell internalization, and dual stimuli activity promotes more cell death. Overall, multifunctional polysaccharides hydrogel nanoconjugates is a prospective material that has great potential for targeting breast cancer therapy., Competing Interests: Conflict of Interest There are no conflicts of interest to declare., (Copyright © 2021 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Balamuthia mandrillaris and Naegleria fowleri are protist pathogens that can cause fatal infections. Despite mortality rate of > 90%, there is no effective therapy. Treatment remains problematic involving repurposed drugs, e.g., azoles, amphotericin B and miltefosine but requires early diagnosis. In addition to drug discovery, modifying existing drugs using nanotechnology offers promise in the development of therapeutic interventions against these parasitic infections. Herein, various drugs conjugated with nanoparticles were developed and evaluated for their antiprotozoal activities. Characterizations of the drugs' formulations were accomplished utilizing Fourier-transform infrared spectroscopy, efficiency of drug entrapment, polydispersity index, zeta potential, size, and surface morphology. The nanoconjugates were tested against human cells to determine their toxicity in vitro. The majority of drug nanoconjugates exhibited amoebicidal effects against B. mandrillaris and N. fowleri. Amphotericin B-, Sulfamethoxazole-, Metronidazole-based nanoconjugates are of interest since they exhibited significant amoebicidal effects against both parasites (p < 0.05). Furthermore, Sulfamethoxazole and Naproxen significantly diminished host cell death caused by B. mandrillaris by up to 70% (p < 0.05), while Amphotericin B-, Sulfamethoxazole-, Metronidazole-based drug nanoconjugates showed the highest reduction in host cell death caused by N. fowleri by up to 80%. When tested alone, all of the drug nanoconjugates tested in this study showed limited toxic effects against human cells in vitro (less than 20%). Although these are promising findings, prospective work is warranted to comprehend the mechanistic details of nanoconjugates versus amoebae as well as their in vivo testing, to develop antimicrobials against the devastating infections caused by these parasites., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In this study, an assay for detection of the cancer biomarker Thomsen-nouvelle (Tn) antigen on the ELISA plates format was designed and developed. The effects of size and the interfacial density of the negative charge of magnetic beads (MBs) on the specific sensitivity of the bioaffinity interaction were studied. In particular, glyconanoconjugate, i.e. glycan Tn antigen conjugated to bovine serum albumin (BSA) was covalently immobilised on MBs for the bioaffinity detection of anti-Tn antibodies as cancer biomarkers. Six different MBs were used in the study, i.e. carboxy-modified MBs of 250 nm, 500 nm, 1000 nm and 2800 nm and epoxy-modified MBs of 2800 nm and 4500 nm. In order to evaluate which MBs are the best suited for detection of the analyte anti-Tn antibodies, sensitivities of detection (slopes from calibration curves) were calculated. Next, specific sensitivities were calculated for each type of MBs as a ratio of sensitivity of detection to the mass of MBs. From zeta potential ζ for each type of MBs, the interfacial charge density on MBs was calculated, expressed as the density of zeta potential ζ d (ratio of zeta potential to surface area of MBs, i.e. ζ d  = ζ/A). Then, we evaluated the effect of size and ζ d on the specific sensitivity of detection of anti-Tn antibodies in order to understand the immobilisation process on nanoscale. We also identified an optimal value of ζ d on MBs; this was essential to achieve highly sensitive detection of the analyte, which made it possible to attain limit of detection (LOD) of (0.31 ± 0.01) ng mL -1 or (2.10 ± 0.04) pM for analyte detection. In addition, the optimal assay configuration was highly selective and enabled reliable detection of the analyte in human serum with a recovery index in the range of 102-104%., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Paclitaxel (PTX) is an essential anticancer drug from the biopharmaceutical classification system (BCS) class IV. Unfortunately, PTX has some drawbacks including low solubility, cell toxicity, adverse cell reaction, etc. Therefore, folic acid (FA) tailored carboxymethyl-dextran (CMD), and bovine serum albumin (BSA) mediated nanoconjugates of paclitaxel (PTX) (FA-CMD-BSA-PTX) were designed. At first, esterification reaction between FA and CMD resulted in FA-CMD conjugate whereas FA-CMD-BSA conjugate was synthesized via the Maillard reaction. Finally, FA-CMD-BSA conjugates of PTX were achieved via hydrophobic interaction and gelation of BSA. Herein, heating offers the gelation of BSA that furnishes the cross-linking wherein PTX gets fixed inside BSA. Thermogram of FA-CMD-BSA-PTX showed the absence of PTX peak that concluding PTX has been molecularly dispersed in polymer matrix and entrapment inside polymeric conjugate. As an effect, surface decorated FA-CMD-BSA-PTX showed low hemolytic toxicity over free PTX. Cytotoxicity assay on A549 human lung cancer cells shows cell viability decreased from 60 % to 10 % with increasing concentration from 1 to 5 μg/mL. In conclusion, CMD facilitates the circulation time of PTX and BSA acts as a carrier to target tumor locations effectively. The nano-conjugate formulation significantly reduces toxicity and can be used for the treatment of lung cancer., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Plant-derived phytoglycogen nanoparticles (PhG NPs) have the advantages of size uniformity, dispersibility in water, excellent lubrication properties, and lack of cytotoxicity; however, their chemical functionalization may lead to loss of NP structural integrity. Here, we report a straightforward approach to the generation of PhG NP conjugates with biologically active molecules. Hydrogen bonding of bovine serum albumin with electroneutral PhG NPs endows them with additional ligand binding affinity and enables the electrostatically governed attachment of methotrexate (MTX), a therapeutic agent commonly used in the treatment of cancer and arthritis diseases, to the protein-capped NPs. We showed stimuli-responsive release of MTX from the PhG-based nanoconjugates under physiological cues such as temperature and ionic strength. The results of this study stimulate future exploration of biomedical applications of nanoconjugates of PhG NPs.

A new hybrid organic-inorganic silsesquioxane material, 3-n-propyl(2-amino-4-methyl)pyridium chloride (SiAMPy + Cl - ), was synthesized and successfully applied for the synthesis of stable nanoconjugates with gold nanoparticles (AuNPs-SiAMPy + ). SiAMPy + Cl - was obtained through a simple sol-gel procedure by using chloropropyltrimetoxysilane and tetraethylorthosilicate as precursors and 2-amino-4-methylpyridine as the functionalizing agent. The resulting material was characterized by employing FTIR, XRD, and 1 H-, 13 C-, and 29 Si-NMR spectroscopy. The synthesis of AuNPs-SiAMPy + nanoconjugates was optimized through a 2 3 full factorial design. UV-VIS, FTIR, TEM, DLS, and ζ-potential measurements were used to characterize the nanoconjugates, which presented a spherical morphology with an average diameter of 5.8 nm. To investigate the existence of toxic effects of AuNPs-SiAMPy + on blood cells, which is essential for their future biomedical applications, toxicity assays on human erythrocytes and leukocytes were performed. Interestingly, no cytotoxic effects were observed for both types of cells. The nanoconjugates were further applied in the construction of electrochemical immunosensing devices, aiming the detection of anti-Trypanosoma cruzi antibodies in serum as biomarkers of Chagas disease. The AuNPs-SiAMPy + significantly enhanced the sensitivity of the biodevice, which was able to discriminate between anti-T. cruzi positive and negative serum samples. Thus, the AuNPs-SiAMPy + -based biosensor showed great potential to be used as a new tool to perform fast and accurate diagnosis of Chagas disease. The promising findings described herein strongly confirm the remarkable potential of SiAMPy + Cl - to obtain nanomaterials, which can present notable biomedical properties and applications., (Copyright © 2022. Published by Elsevier B.V.)

Spherical gold nanoparticles (GNPs), whose unique properties regarding biomedical applications were broadly investigated, are an object of interest as nanocarriers in drug targeted delivery systems (DTDSs). The possibility of surface functionalization, especially in enabling longer half-life in the bloodstream and enhancing cellular uptake, provides an opportunity to overcome the limitations of popular anticancer drugs (such as cisplatin) that cause severe side effects due to their nonselective transportation. Herein, we present investigations of gold nanoparticle-cisplatin systems formation (regarding reaction kinetics and equilibrium) in which it was proved that the formation efficiency and stability strongly depend on the nanoparticle surface functionalization. In this study, the capillary electrophoresis hyphenated with inductively coupled plasma tandem mass spectrometry (CE-ICP-MS/MS) was used for the first time to monitor gold-drug nanoconjugates formation. The research included optimizing CE separation conditions and determining reaction kinetics using the CE-ICP-MS/MS developed method. To characterize nanocarriers and portray changes in their physicochemical properties induced by the surface's processes, additional hydrodynamic size and ζ-potential by dynamic light scattering (DLS) measurements were carried out. The examinations of three types of functionalized GNPs (GNP-PEG-COOH, GNP-PEG-OCH 3 , and GNP-PEG-biotin) distinguished the essential differences in drug binding efficiency and nanoconjugate stability.

Targeted drug delivery by nanocarriers molecules can increase the efficiency of cancer treatment. One of the targeting ligands is folic acid (FA), which has a high affinity for the folic acid receptors, which are overexpressed in many cancers. Herein, we describe the preparation of the nanoconjugates containing quantum dots (QDs) and β -cyclodextrin ( β -CD) with foliate-targeting properties for the delivery of anticancer compound C-2028. C-2028 was bound to the nanoconjugate via an inclusion complex with β -CD. The effect of using FA in QDs- β -CD(C-2028)-FA nanoconjugates on cytotoxicity, cellular uptake, and the mechanism of internalization in cancer (H460, Du-145, and LNCaP) and normal (MRC-5 and PNT1A) cells was investigated. The QDs- β -CD(C-2028)-FA were characterized using DLS (dynamic light scattering), ZP (zeta potential), quartz crystal microbalance with dissipation (QCM-D), and UV-vis spectroscopy. The conjugation of C-2028 with non-toxic QDs or QDs- β -CD-FA did not change the cytotoxicity of this compound. Confocal microscopy studies proved that the use of FA in nanoconjugates significantly increased the amount of delivered compound, especially to cancer cells. QD green - β -CD(C-2028)-FA enters the cells through multiple endocytosis pathways in different levels, depending on the cell line. To conclude, the use of FA is a good self-navigating molecule in the QDs platform for drug delivery to cancer cells.

In this paper, magnetic molecularly imprinted nano-conjugates were synthesized to serve as selective sorbents in a model study of tyramine determination in craft beer samples. The molecularly imprinted sorbent was characterized in terms of morphology, structure, and composition. The magnetic dispersive solid phase extraction protocol was developed and combined with liquid chromatography coupled with mass spectrometry to determine tyramine. Ten samples of craft beers were analyzed using a validated method, revealing tyramine concentrations in the range between 0.303 and 126.5 mg L -1 . Tyramine limits of detection and quantification were 0.033 mg L -1 and 0.075 mg L -1 , respectively. Therefore, the fabricated molecularly imprinted magnetic nano-conjugates with a fast magnetic responsivity and desirable adsorption performance could be an effective tool for monitoring tyramine levels in beverages.

Acute myeloid leukemia (AML) is a highly aggressive type of cancer caused by the uncontrolled proliferation of undifferentiated myeloblasts, affecting the bone marrow and blood. Systemic chemotherapy is considered the primary treatment strategy; unfortunately, healthy cells are also affected to a large extent, leading to severe side effects of this treatment. Targeted drug therapies are becoming increasingly popular in modern medicine, as they bypass normal tissues and cells. Two-dimensional MoS 2 -based nanomaterials have attracted attention in the biomedical field as promising agents for cancer diagnosis and therapy. Cancer cells typically (over)express distinctive cytoplasmic membrane-anchored or -spanning protein-based structures (e.g., receptors, enzymes) that distinguish them from healthy, non-cancerous cells. Targeting cancer cells via tumor-specific markers using MoS 2 -based nanocarriers loaded with labels or drugs can significantly improve specificity and reduce side effects of such treatment. SKM-1 is an established AML cell line that has been employed in various bio-research applications. However, to date, it has not been used as the subject of studies on selective cancer targeting by inorganic nanomaterials. Here, we demonstrate an efficient targeting of AML cells using MoS 2 nanoflakes prepared by a facile exfoliation route and functionalized with anti-CD33 antibody that binds to CD33 receptors expressed by SKM-1 cells. Microscopic analyses by confocal laser scanning microscopy supplemented by label-free confocal Raman microscopy proved that (anti-CD33)-MoS 2 conjugates were present on the cell surface and within SKM-1 cells, presumably having been internalized via CD33-mediated endocytosis. Furthermore, the cellular uptake of SKM-1 specific (anti-CD33)-MoS 2 conjugates assessed by flow cytometry analysis was significantly higher compared with the cellular uptake of SKM-1 nonspecific (anti-GPC3)-MoS 2 conjugates. Our results indicate the importance of appropriate functionalization of MoS 2 nanomaterials by tumor-recognizing elements that significantly increase their specificity and hence suggest the utilization of MoS 2 -based nanomaterials in the diagnosis and therapy of AML., (© 2021 IOP Publishing Ltd.)

Recently, we designed an inventive paradigm in nanomedicine-drug-free macromolecular therapeutics (DFMT). The ability of DFMT to induce apoptosis is based on biorecognition at cell surface, and crosslinking of receptors without the participation of low molecular weight drugs. The system is composed of two nanoconjugates: a bispecific engager, antibody or Fab' fragment-morpholino oligonucleotide (MORF1) conjugate; the second nanoconjugate is a multivalent effector, human serum albumin (HSA) decorated with multiple copies of complementary MORF2. Here, we intend to demonstrate that DFMT is a platform that will be effective on other receptors than previously validated CD20. We appraised the impact of daratumumab (DARA)- and isatuximab (ISA)-based DFMT to crosslink CD38 receptors on CD38+ lymphoma (Raji, Daudi) and multiple myeloma cells (RPMI 8226, ANBL-6). The biological properties of DFMTs were determined by flow cytometry, confocal fluorescence microscopy, reactive oxygen species determination, lysosomal enlargement, homotypic cell adhesion, and the hybridization of nanoconjugates. The data revealed that the level of apoptosis induction correlated with CD38 expression, the nanoconjugates meet at the cell surface, mitochondrial signaling pathway is strongly involved, insertion of a flexible spacer in the structure of the macromolecular effector enhances apoptosis, and simultaneous crosslinking of CD38 and CD20 receptors increases apoptosis.

Tumors are complex and highly variable, making it difficult for a single treatment strategy to be significantly effective for cancer therapy. Herein, we report a robust cascade biomimetic nanoplatform that integrates chemiluminescence-induced photodynamic therapy (CL-PDT), Fenton reaction-based chemodynamic therapy (CDT), and glucose oxidase (GOD)-mediated starvation therapy to synergistically enhance cancer treatment. For the nanoplatform of CPPO@porphyrin-MOF@Cancer cell membrane-GOD (C1@M@C2G), the ferric ion-linked porphyrin-MOF can trigger a Fenton reaction to reach CDT, the carried CPPO as an energy donor is used to excite a photo-sensitive porphyrin-MOF in situ to generate singlet oxygen (1O2) for PDT, GOD catalyzes glucose into H2O2 and gluconic acid to realize starvation therapy, and the cancer cell membrane wrapped onto the nanoparticle plays a key role in homologous targeting, which is conducive to achieving better therapeutic effects. Significantly, the porphyrin-MOF with catalase-like activity can generate O2 to effectively relieve tumor hypoxia, thereby enhancing the catalytic effect of GOD and the efficacy of PDT. Additionally, the produced H2O2 and gluconic acid can further improve the CPPO-H2O2-triggered CL-PDT and promote the low pH-dependence Fenton reaction-based CDT, respectively. Both in vitro and in vivo studies showed that the constructed nanoplatform displays an excellent cooperative anti-tumor performance, so we firmly believe that this simple nanoplatform broadens the pathway to fight against cancer through effective cascade catalysis.

The Ibuprofen-Cellulose nanofibril (IBU-CNF) drug delivery system was prepared by esterification of Ibuprofen (IBU) and cellulose nanofibril (CNF) with isopropyl acetate as the solvent and sulfuric acid as the catalyst. The results showed that IBU was successfully grafted on to the CNF molecular chain and the crystal structure of CNF did not change. Moreover, the natural three-dimensional network structure was maintained to a large extent. The maximum drug loading of IBU-CNF was 151.38 mg/g. In vitro drug release showed that IBU-CNF was pH-responsive and could be released continuously over 24 h. The cumulative release rate was approximately 90% under alkaline conditions but was low under acidic conditions. UV-visible spectra revealed that IBU retained its chemical activity after in vitro release., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In this study, a high molecular weight arabinoxylan (AX, Mw: 694 kDa) from wheat bran was alkaline extracted and covalently linked with Catechin (CA) by free radical catalytic reaction. Comparing to AX, arabinoxylan-catechin (AX-CA) conjugates demonstrated an extra UV-vis absorption peak at 274 nm, a new FT-IR absorption band at 1516 cm -1 and new proton signals at 6.5-7.5 ppm, which all confirmed the covalently linked structure. Grafting CA onto AX not only decreased the molecular weight, thermal stability and apparent viscosity of AX, but also enhanced its inhibition effects on starch digestibility in vitro. The in vitro fermentation test with pig feces showed that the degradation & utilization rate of AX, the total short-chain fatty acid (SCFA) and acetic acid levels produced all were significantly delayed after grafting. This study provided a novel approach to synthesize AX-CA conjugates that could be a novel dietary fiber of enhanced functional/bioactive properties using in the fields of functional foods and medicine., (Copyright © 2021 Elsevier B.V. All rights reserved.)

This study presents a novel, economical, and environmentally technique for synthesizing magnetic palladium complex conjugated to activated calcium lignosulfonate with triethylenetetramine (Fe 3 O 4 @lignosulfonate@triethylenetetramine@Pd complex (FLT-Pd complex)) as a practical and air-stable catalyst. FLT-Pd complex is used as a catalyst for the fabrication of 4-methyl-N-phenyl-benzenesulfonamide derivatives via N-arylation of 4-methylbenzenesulfonamide in good yields. Furthermore, because of the complex magnetic reparability and high stability, it could be removed easily from the reaction media using a magnet and reused 5 cycles without a remarkable loss of catalytic prowess., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Reaction centers (RCs) are the pivotal component of natural photosystems, converting solar energy into the potential difference between separated electrons and holes that is used to power much of biology. RCs from anoxygenic purple photosynthetic bacteria such as Rhodobacter sphaeroides only weakly absorb much of the visible region of the solar spectrum, which limits their overall light-harvesting capacity. For in vitro applications such as biohybrid photodevices, this deficiency can be addressed by effectively coupling RCs with synthetic light-harvesting materials. Here, we studied the time scale and efficiency of Förster resonance energy transfer (FRET) in a nanoconjugate assembled from a synthetic quantum dot (QD) antenna and a tailored RC engineered to be fluorescent. Time-correlated single-photon counting spectroscopy of biohybrid conjugates enabled the direct determination of FRET from QDs to attached RCs on a time scale of 26.6 ± 0.1 ns and with a high efficiency of 0.75 ± 0.01.

Background: Photodynamic therapy (PDT) may elicit antitumor immune response in addition to killing cancer cells. However, PDT as a monotherapy often fails to induce a strong immunity. Immune checkpoint inhibitors, which selectively block regulatory axes, may be used in combination with PDT to improve treatment outcomes. Indoleamine 2,3-dioxygenase (IDO) is an immunoregulatory enzyme and an important meditator of tumor immune escape. Combination therapy with PDT and IDO-targeted immune checkpoint blockage is promising but has been seldom been explored., Methods: Herein we report a composite nanoparticle that allows for simultaneous delivery of photosensitizer and IDO inhibitor. Briefly, we separately load ZnF 16 Pc, a photosensitizer, and NLG919, an indoleamine 2,3-dioxygenase (IDO) inhibitor, into ferritin and poly(lactide-co-glycolic)-block-poly(ethylene glycol) (PEG-PLGA) nanoparticles; we then conjugate these two compartments to form a composite nanoparticle referred to as PPF NPs. We tested combination treatment with PPF NPs first in vitro and then in vivo in B16F10-tumor bearing C57/BL6 mice., Results: Our results showed that PPF NPs can efficiently encapsulate both ZnF 16 Pc and NLG919. In vivo studies found that the combination treatment led to significantly improved tumor suppression and animal survival. Moreover, the treatment increased tumor infiltration of CD8 +  T cells, while reducing frequencies of MDSCs and Tregs. 30% of the animals showed complete tumor eradication, and they successfully rejected a second tumor inoculation. Overall, our studies introduce a unique composite nanoplatform that allows for co-delivery of photosensitizer and IDO inhibitor with minimal inter-species interference, which is ideal for combination therapy.

Anti-cancer strategies using nanocarrier systems have been explored in a variety of cancers; these systems can easily be incorporated into tumors via the enhanced permeability and retention (EPR) effect leading to enhanced anti-tumor activity while reducing systemic toxicity by specific tumor-targeting. The prognosis of hepatocellular carcinoma (HCC) is extremely poor when the condition is diagnosed at the unresectable stage as treatment options are limited. In order to improve the treatment of cancer and the overall anti-cancer effect, polymerized phenylboronic acid conjugated doxorubicin (pPBA-Dox) nanocomplexes were generated, and conjugated doxorubicin, which is conventionally used in HCC. The nanocomplexes exhibited enhanced anti-tumor activity via tumor-specific targeting in the subcutaneous and orthotopic HCC syngeneic mice tumor model, implying that the nanocomplexes facilitate the targeted Dox delivery to liver cancer in which the sialic acid is over-expressed. Therefore, this study provides insight into the novel targeted therapy using the nanocomplexes for the treatment of HCC., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Rectangular V-amylose single crystals were prepared by adding racemic ibuprofen to hot dilute aqueous solutions of native and enzymatically-synthesized amylose. The lamellar thickness increased with increasing degree of polymerization of amylose and reached a plateau at about 7 nm, consistent with a chain-folding mechanism. The CP/MAS NMR spectrum as well as base-plane electron and powder X-ray diffraction patterns recorded from hydrated specimens were similar to those of V-amylose complexed with propan-2-ol. Amylose was crystallized in an orthorhombic unit cell with parameters a = 2.824 ± 0.001 nm, b = 2.966 ± 0.001 nm, and c = 0.800 ± 0.001 nm. A molecular model was proposed based on structural analogies with the V propan-2-ol complex and on assumptions on the stoichiometry of ibuprofen. The unit cell would contain four antiparallel 7-fold amylose single helices with ibuprofen molecules distributed inside and between the helices., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Alcohol abuse induces the expression of inflammatory mediators by activating the immune receptors to trigger neuroinflammation and brain damage; however, therapies that reduce neuroimmune system activation may protect against alcohol's damaging effects. Curcuminoids possess anti-inflammatory properties but suffer from low bioavailability; therefore, we designed a new receptor-targeted biodegradable star-shaped crosslinked polypeptide polymer that bears propargylamine moieties and bisdemethoxycurcumin (StClPr-BDMC-ANG) as an enhanced anti-inflammatory therapeutic that penetrates the blood-brain-barrier and ameliorates alcohol-induced neuroinflammation. StClPr-BDMC-ANG administration maintains the viability of primary glia and inhibits the ethanol-induced upregulation of crucial inflammatory mediators in the prefrontal and medial cortex in a mouse model of chronic ethanol consumption. StClPr-BDMC-ANG treatment also suppresses the ethanol-mediated downregulation of microRNAs known to negatively modulate neuroinflammation in the brain cortex (miRs 146a-5p and let-7b-5p). In summary, our results demonstrate the attenuation of alcohol-induced neuroinflammation by an optimized and targeted polypeptide-based nanoconjugate of a curcuminoid., Competing Interests: Conflict of interest A.D-C and M.J.V declare that a patent with reference WO2017025298A1 has been filed related to the present work. The rest of the authors declare no conflict of interest and no currently commercial association within the past five years., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Saussurea laniceps Hand.-Mazz. (Compositae) is a representative "snow lotus" herb well known in Chinese folk medicine to treat inflammation-related diseases such as arthritis. S. laniceps (SL) shows anti-inflammatory and analgesic potencies and contains various constituents potentially with cyclooxygenase-2 (COX-2) selective inhibition. The herb is a valuable source of natural alternatives to synthetic COX-2 selective nonsteroidal anti-inflammatory drugs, a common medication for rheumatoid arthritis (RA) and osteoarthritis (OA) reported with serious cardiovascular side effects., Aim of the Study: Based on an innovative drug screening platform, this study aimed to discover safe, effective COX-2 selective inhibitors from SL., Materials and Methods: An enzyme-anchored nanomagnetic fishing assay was developed to separate COX-2 ligands from SL. Cell and animal models of cardiomyocytes, lipopolysaccharide-stimulated macrophages, rat adjuvant-induced arthritis, and anterior cruciate ligament transection-induced OA rats, were adopted to screen the single/combined ligands regarding toxicity and bioactivity levels. Molecular docking was employed to unravel binding mechanisms of the ligands towards COX-1 and COX-2., Results: Four COX-2 selective compounds were separated from SL using optimized COX-2-functionalized magnetic nanoparticles. All the four ligands were proved with evidently lower cardiotoxicity both in vitro and in vivo than celecoxib, a known COX-2 selective inhibitor. Two ligands, scopoletin and syringin, exhibited potent anti-arthritic activities in rat models of RA and OA by alleviating clinical statuses, immune responses, and joint pathological features; their optimum combination ratio was discovered with stronger remedial effects on rat OA than single administrations. The COX-1/2 binding modes of the two phytochemicals contributed to explain their cardiac safety and therapeutic performances., Conclusions: The screened chemicals are promising to be developed as COX-2 selective inhibitors as part of treating RA and OA. The hybrid strategy for discovering therapeutic agents from SL is shown here to be efficient; it should be equally valuable for finding other active chemicals in other natural sources., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Emergence of nanotechnology created a drastic change in the field of cancer therapy due to their unique features in drug delivery and imaging. Polysaccharide based nanoparticles have received extensive attention in recent years as promising nanoparticle mediated drug delivery systems. Polysaccharides are endorsed with versatile merits including high drug encapsulation efficiency, efficient drug protection against chemical or enzymatic degradation, unique ability to create a controlled release and cellular internalization. In the current study, we have fabricated doxorubicin-loaded carboxymethylated PST001 coated iron oxide nanoparticles (DOX@CM-PST-IONPs) for better management of cancer. CM-PST coated iron oxide nanoparticles co-encapsulated with chemotherapeutic drug doxorubicin, can be utilized for targeted drug delivery. Biocompatible and non-toxic nanoconjugates was found to be effective in both 2-D and 3-D cell culture system with efficient cancer cell internalization. The bench-marked potential of CM-PIONPs to produce reactive oxygen species makes it a noticeable drug delivery system to compact neoplasia. These nanoconjugates can lay concrete on a better way for the elimination of cancer spheroids and tumor burden.