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The development of effective drug delivery systems is crucial for improving cancer treatment outcomes. A promising carrier using a combination of DNA and exosomes (EXO) was synthesized to sustain the release of the powerful anticancer drug 5‐fluorouracil (5‐FU). The carrier was prepared by encapsulating 5‐FU‐loaded exosomes (5‐FU.EXO) in the heated DNA carriers (5‐FU.EXO@DNA). Alteration of the DNA structure was studied using molecular dynamics. The physicochemical properties of the carriers were characterized using fourier‐transform infrared spectroscopy (FTIR), field‐emission scanning electron microscopy (FESEM), and dynamic light scattering (DLS). The 5‐FU.EXO@DNA carrier exhibited good stability and biocompatibility, with a uniform size distribution (709±269 nm) and a zeta potential of +312 mV. The interaction between 5‐FU and DNA was confirmed using molecular docking. In vitro release studies showed that both 5‐FU@DNA and 5‐FU.EXO@DNA carriers achieved sustained release of 5‐FU for 576 h, with cumulative releases of approximately 83 % and 89 %, respectively. The 5‐FU release profile showed 40 % release over 86 h. The release rate and other kinetic parameters were also determined. Furthermore, the release kinetics followed by the Korsmeyer‐Peppas model and the diffusion mechanism plays a significant role in controlling the release process. [ABSTRACT FROM AUTHOR]

IntroductionCancer is a deadly disease and the second most common cause of death after cardiovascular disease. Various factors are responsible for the increasing incidence of cancer, of which modernization of [...], The aim of this study was to examine the interaction of [Pd (2,2'-bipyridine) (morpholinedithiocarbamate)] N[O.sub.3] and [Pt (2,2'-bipyridine)(morpholinedithiocarbamate)]N[O.sub.3] with human serum albumin under physiological conditions by using fluorescence, absorption, and circular dichroism spectroscopic techniques. Spectroscopic analysis of the emission quenching at different temperatures demonstrated that the quenching mechanism was static quenching. From the circular dichroism results, thermal stability study, it was found that the interaction of the complexes with human serum albumin caused a conformational change of the protein reversibly. These 2 anticancer Pd and Pt complexes were activated against chronic myelogenous leukemia cell line K562, so that 50% cytotoxic concentration values of 16 and 26 [micro]M for Pd and Pt complexes, respectively, were observed, which were much lower than that of cisplatin (154 [micro]M). Biological activities of both Pd and Pt complexes were also assayed against selective microorganisms by the disc diffusion method. These results showed that the Pd(II) complex is antifungal agent but Pt(II) complex has antibacterial activity. Also, the interaction of both metal derivative complexes was studied by molecular docking. Complementary molecular docking results may be useful to determine the binding mechanism of human serum albumin in pharmaceutical and biophysical studies providing new insight in the novel pharmacology.Key words: dithiocarbamate, Pt and Pd complexes, HSA binding, fluorescence and circular dichroism spectroscopy, antifungal and antibacterial activity, molecular docking.Cette etude a pour but d'examiner l'interaction des complexes [Pd(2,2'-bipyridine) (morpholinedithiocarbamate)] N[O.sub.3] et [Pt (2,2'-bipyridine) (morpholinedithiocarbamate)] N[O.sub.3] avec l'albumine serique humaine (ASH) en conditions physiologiques, a l'aide de techniques spectroscopiques de fluorescence, d'absorption et de dichroisme circulaire. L'analyse spectroscopique de l'extinction de remission a differentes temperatures a montre que le mode d'action de l'extinction etait de nature statique. A partir des resultats sur le dichroisme circulaire, l'etude de stabilite thermique, nous avons observe que l'interaction entre les complexes et l'ASH provoquait un changement conformationnel reversible de la proteine. Ces deux complexes Pd et Pt anticancereux etaient actifs contre des lignees cellulaires K562 de leucemie myeloide chronique, de telle sorte que nous observions des valeurs de concentrations demi-cytotoxiques des complexes Pd et Pt de 16 et de 26 [micro]M, respectivement, ce qui correspond a des chiffres beaucoup moins eleves qu'avec le cisplatine (154 [micro]M). A l'aide de la methode de diffusion sur disque, nous avons aussi etudie l'activite biologique des complexes Pd et Pt contre des microorganismes selectifs. Ces resultats ont montre que le complexe Pd(II) correspond a un agent antifongique, mais que le complexe Pt(II) est dote d'une activite antibacterienne. En outre, nous avons etudie l'interaction avec les deux complexes derives de metaux a l'aide de techniques d'arrimage moleculaire. Les resultats complementaires avec l'arrimage moleculaire pourraient se reveler etre utiles en vue d'etablir les modes d'action de la liaison avec l'ASH dans le cadre d'etudes pharmaceutiques et biophysiques permettant d'obtenir de nouvelles donnees pouvant contribuer a l'innovation en pharmacologie. [Traduit par la Redaction]Mots-cles: dithiocarbamate, complexes Pt et Pd, liaison a l'albumine serique humaine, spectroscopie par fluorescence et dichroisme circulaire, activite antifongique et antibacterienne, arrimage moleculaire.

Background: To overcome cisplatin resistance, the cytotoxicity of a novel antitumor agent on two ovarian cancer cell lines sensitive and resistant to cisplatin was investigated. Methods: MTT assay and flow cytometry were performed to assess the cytotoxicity of a novel water-soluble Pd (II) complex, [Pd(bpy)(pyr-dtc)]NO3 (PBPD), on cisplatin-sensitive and cisplatin-resistant ovarian cancer cell lines. Furthermore, variations in the expression of drug resistance gene cluster of differentiation 99 (CD99), signal transducer and activator of transcription 3 (STAT3), octamer-binding transcription factor 4 (OCT4), and multidrug resistance mutation 1 (MDR1) were evaluated using Real-Time PCR. Results: The IC50 values of PBPD in resistant cells were higher than those in sensitive cells. Furthermore, PBPD has a deadlier effect on sensitive cells compared to resistant cells, and the cell survival rate is reduced over time. Flow cytometry revealed that PBPD enhanced the population of living-resistant cells while driving them to apoptosis. PBPD, on the other hand, has a greater effect on the living cell population and has dramatically shifted the population toward apoptosis and necrosis in the sensitive cells. Furthermore, gene expression analysis showed that when sensitive and resistant cells were treated with cisplatin, all resistance genes increased significantly relative to the control. In contrast to OCT4, MDR1, STAT3, and CD99 resistance genes were not significantly elevated in sensitive cells treated with PBPD compared to the control. Thus, the expression of resistance genes in resistant cells treated with PBPD was lower than cisplatin. Conclusions: As a result, PBPD is a promising anticancer agent for CDDP-resistant ovarian cancer. [ABSTRACT FROM AUTHOR]

In recent years, much effort has been devoted to designing nanoparticle drug delivery systems and improving the efficacy of anticancer drugs. This study focused on the preparation of a novel biocompatible nanocarrier based on bacterial cellulose (BC) in the presence of exosome (Exo) for the controlled release of 5‐fluorouracil (5‐FU), known as 5‐FU.Exo@BC. The physicochemical properties of 5‐FU.Exo@BC were thoroughly characterized using field emission scanning electron microscopy (FESEM), differential scanning calorimetry (DSC), Fourier‐transform infrared spectroscopy (FTIR), and X‐ray diffraction (XRD). These results confirmed the successful preparation of 5‐FU.Exo@BC. The release behavior of 5‐FU.Exo@BC compared with 5‐FU and 5‐FU@BC demonstrated a significant sustained release over 162 h. The release mechanism of the above three systems followed Korsmeyer‐Peppas with non‐Fickian diffusion for 5‐FU@BC and 5‐FU.Exo@BC. Furthermore, the viability of HT‐29 cells (human colon cancer cell lines) against BC, 5‐FU@BC and 5‐FU.Exo@BC indicated that 5‐FU has promising efficacy in 5‐FU.Exo@BC system. Subsequently, the prepared bio‐nanocomposite could be suggested as a potential drug delivery system with an effective controlled‐release function. [ABSTRACT FROM AUTHOR]

Background: Despite remarkable progress in bone regenerative medicine, developing a cost effective approach for osteocyte regeneration on matrixes with proper three-Dimensional (3D) morphological form and mechanical strength is still challenging. Finding a proper scaffold having optimized parameters such as chemical composition, mechanical properties and surface characteristics can improve bone repairing and regeneration for clinical applications. Stone paper (also known as mineral paper) is a new type of papers that consists of calcium carbonate and High-density Polyethylene (HDPE) that has great potential to be introduced as a cost-effective composite for bone tissue engineering applications. Here, we aimed to develop a feasible platform to improve artificial bone generation that ia capable of mimicking bone tissue microenvironment. In this regard, patterned stone paper with laser ablation was evaluated for bone tissue engineering purposes. Moreover, to improve hydrophilicity and consequent cell regeneration, polydopamine coating was examined on patterned surfaces. Materials and Methods: Two different designs were selected to be ablated using CO2 Laser for using as 3D matrix for bone regeneration. The ablated papers were then immersed in a solution in order to be coated with polydopamine. Physicochemical characterization of obtained scaffolds was performed using XRD, SEM, ATR and WCA to verify both effects of laser ablation and surface modification. Also, MTT test was done to determine the level of cytotoxicity. Results: XRD test proved that the laser process didn't have any destructive effect on the crystal structure of calcium carbonate in mineral paper scaffold. We have optimized patterns of laser ablation based on data obtained by the SEM less distortions and cracks. Although the water contact angle of the paper has been increased about 30 degrees after laser ablation process, coating the paper with polydopamine has positive effects on surface roughness, wettability, porosity, mechanical properties, and specific surface area. Structural characterization of the scaffolds by ATR demonstrated that polydopamine coating had significant effect on physicochemical properties of matrix mainly in interconnected pores without any toxicity confirmed by MTT assay. Conclusion: Based on obtained results, it can be concluded that the surface modified laser ablated rich mineral paper scaffold has great potential for promoting cell proliferation and osteogenic differentiation. Combination physical and chemical modification by Co2 laser ablation and polydopamine coating have led to improved scaffold properties for future clinical applications. [ABSTRACT FROM AUTHOR]

Novel studies have shown neurological treatment possibilities with extracellular vesicles (EVs) as natural particles with a special composition that are produced by different cell types. Their stability, natural structure, composition, and bioavailability make them good candidates as drug vehicles. Here, EVs were isolated from amniotic fluid (AF) through differential centrifugation, and characterized for size (<200 nm), structure, and composition, their effectiveness on the human PC12 cell line, and brain of chick embryos exposed to sodium valproate (animal autistic model). Sulforaphane (SFN) was employed as a bioactive compound and then encapsulated into Evs using three methods including passive (incubation), active (sonication), and active‐passive (sonication‐incubation). Further, the loading and in vitro releases of SFN fitted the Korsmeyer–Peppas (R2 = 0.99) kinetic model by non‐Fickian diffusion case II (n = 0.44, passive loading) and Fickian diffusion case I (n = 0.41, active and active‐passive loading). SFN‐loaded EVs (SFN@EVs; 11 μM: 103 nM) stimulated hPC‐12 cell proliferation. The gene expression analysis revealed that SFN@EVs could upregulate Nrf2 and reduce IL‐6 expression. Eventually, histopathological results of the coronal cross‐section of the chick embryos brain showed treatment with SFN@EVs. This treatment illustrated normality in the gray and white matter and the orientation of the bipolar neurons. Our findings showed EVs' potentially acting as a gene expression regulator in autism spectrum disorder. [ABSTRACT FROM AUTHOR]

The synthesis of a new palladium(II) complex, [Pd(AMTTO)(PPh3)2] (1, H2AMTTO = 4-amino-6-methyl-1,2,4-triazine-3-thione-5-one), is reported. Complex 1 has been characterized by FT-IR, 1H NMR and 31P NMR spectroscopy as well as mass spectrometry. Furthermore, its molecular structure and thermal stability have been investigated via X-ray and thermogravimetric analyses. The crystal structure of 1 revealed that the twofold deprotonated ligand acts as a bidentate chelating one and coordinates to the metal ion through its sulfur and nitrogen atoms in a cis-arrangement. The biological activity including anticancer and antibacterial activity of the ligands and complex 1 was studied. The IC50 value of the latter against MCF-7 was 0.06 mM. This is while carboplatin (as a standard anticancer drug) exhibited no cytotoxicity at the same concentration. Moreover, the synthesized Pd(II) complex displayed potent antimicrobial activity against Gram-positive (ATCC 6538) and Gram-negative (ATCC 25922) bacterial strains. [ABSTRACT FROM AUTHOR]

With the aim of cancer treatment, interaction between 1-hexyldithiocarbamato 1,10-phenanthrolinepalladium(II) nitrate complex ([Pd(Hex-Dtc)(Phen)]NO3, Pd-HDP), as a potential antitumor candidate and human serum albumin (HSA), was investigated at four temperatures under physiological conditions. The cell viability of Pd-HDP on normal cell lines, HFFF2 and cancer cell lines, HeLa, and G-292 were also tested. Changes in fluorescence intensity, 3D-fluorescence, synchronous fluorescence, absorption, and circular dichroism spectra of HSA were due to binding with Pd-HDP. The quenching mechanism was suggested as a combination of dynamic and static. The binding constant (K × 104) and the number of binding sites (n ≈ 1) were also determined. Thermodynamic parameters proved that the interaction process was spontaneous (ΔG < 0) and van der Waals interaction and hydrogen bonding were the predominant binding in HSA-Pd-HDP system (ΔH < 0 and ΔS < 0). Moreover; the binding distance between Pd-HDP and the tryptophan residue of HSA was studied according to Forster resonance energy transfer (FRET) theory. The site marker competitive results revealed that Pd-HDP bind to Sudlow's site II of albumin. Furthermore; molecular docking results agreed with the results of thermodynamic and spectroscopic study. [ABSTRACT FROM AUTHOR]

Two novel palladium(II)–amino acid complexes, [Pd(Ala)2]·H2O (PA) and [Pd(Val)2].H2O (PV) (Ala = alanine; Val = valine) were synthesized and characterized through FTIR, UV/Vis, 1H-NMR spectroscopies, CHN analysis, X-ray crystallography and molar conductivity measurement. Furthermore, cytotoxicity of Pd(II) complexes against human leukemia cancer cell line, MOLT4 showed promising cancer cell death (CC50 = 0.71 ± 0.046 µM for PA; CC50 = 0.85 ± 0.063 µM for PV) that were less than cisplatin (1.59 ± 0.25 µM). Moreover, the interaction of both the complexes with DNA and BSA was studied using UV–Vis absorption and emission spectroscopic techniques that demonstrated the bindings occurred via van der Waals forces and hydrogen bond. Furthermore, the fluorescence titration showed that static quenching mechanism plays predominate role in binding process. All results showed that both complexes have more binding tendency to DNA in compared to BSA that can be a significant achievement for further medical purposes as a potential antitumor candidate. Finally, molecular docking simulation was performed for PA and PV complexes with DNA and BSA and demonstrated both complexes bind to the groove of DNA mainly by hydrogen bond and interact with site I of BSA via hydrogen bond as well. [ABSTRACT FROM AUTHOR]

A novel mononuclear palladium(II) complex, [Pd(L)Cl2]·DMF (1·DMF, L = 1,4-bis(5-amino-1,3,4-thiadiazol-2-sulfanyl-methyl)benzene), has been synthesized and characterized by elemental analysis, FT-IR and 1H NMR spectroscopy and single-crystal X-ray diffraction. On the basis of the molecular structure, in 1·DMF, a ligand acts as a bidentate chelating one using its endocyclic nitrogen atoms. The biological activities of the free ligand and its palladium complex including cytotoxic activity towards the human colon cancer cell line (HCT-116) and antibacterial activity against one Gram-negative strain (Escherichia coli (ATCC 25922)) and one Gram-positive strain (Staphylococcus aureus (ATCC 6538)) have been examined. The IC50 value of 1·DMF against HCT-116 was 500 μM, which is much higher than that reported for cisplatin, and hence, the compound exhibited low anticancer efficacy compared to cisplatin. However, it exhibited excellent antibacterial activities against both Gram-negative as well as Gram-positive bacterial microorganisms. Furthermore, the thermal stability of complex 1·DMF was studied by thermal gravimetric analysis (TGA). The resulting product was characterized as highly pure PdO nanoparticles (mean crystallite size: 39 nm) by using a series of techniques including powder XRD, EDAX, and SEM. [ABSTRACT FROM AUTHOR]

Correction for 'In vitro and in vivo antiproliferative activity of organo-nickel SCS-pincer complexes on estrogen responsive MCF7 and MC4L2 breast cancer cells. Effects of amine fragment substitutions on BSA binding and cytotoxicity' by Mahboubeh Hosseini-Kharat et al., Dalton Trans., 2018, 47, 16944–16957, https://doi.org/10.1039/c8dt03079k. [ABSTRACT FROM AUTHOR]

To sustained release of an anticancer drug, oxaliplatin (OX), a non‐toxic and biocompatible nanocarrier based on bovine serum albumin (BSA) were synthesised by desolvation method and characterised using Fourier‐transform infrared (FTIR) spectroscopy, field emission scanning electron microscopy (FESEM), atomic force microscopy (AFM) and dynamic light scattering. The results showed that the BSA nanoparticles (BSANPs) with a mean magnitude of 187.9 ± 1.2 nm have spherical morphology with a smooth surface and a uniform distribution. Furthermore, OX was loaded onto the BSANPs and the loading was confirmed by FTIR, AFM and FESEM techniques. The percentage of encapsulation efficiency and drug loading were determined by absorption spectroscopy (UV–vis). The drug release studies showed that release of OX from BSANPs exhibited slower release rate. However, the release kinetics followed the first‐order kinetic for both of them with the non‐Fickian release behaviour. The electrochemical analysis showed stability of OX loaded onto the BSANPs (OX@BSANPs) and confirmed the diffusion mechanism. Furthermore, the results of MTT assay revealed increasing of normal cell viability and cancer cell death in the OX@BSANPs compared to only OX. It was shown that the BSANPs could be safely used as a biocompatible nanocarrier for the sustained release of OX. [ABSTRACT FROM AUTHOR]

[Zn(ph-dtc)(bpy)]Cl (1) and [Zn(ph-dtc)(phen)]Cl (2) (where bpy = 2,2′-bipyridine, phen = 1,10-phenanthroline and ph-dtc = phenylacetichydrazidedithiocarbamate) were synthesized and characterized by elemental analysis and spectroscopic methods (FT–IR, UV–Vis and 1H NMR). Zn(II) complexes were examined in biological tests in vitro using MCF-7 breast cancer cell line. Both complexes showed significant cytotoxic activity against human breast cancer MCF-7 cells. The interaction of above compounds with Human Serum Albumin (HSA) was investigated by means of various spectroscopic (at pH ∼ 7.4 in Tris–HCl buffer medium) and molecular docking methods. The fluorescence data showed that 1 and 2 quench the intrinsic fluorescence of HSA through a static quenching procedure. The binding constants (Kb) and the number of binding sites (n ∼ 1) were calculated. The thermodynamic analysis suggested that hydrophobic interaction played major roles in the binding of 1 or 2 to HSA. The distance r between protein and the above-mentioned compounds was obtained according to fluorescence resonance energy transfer. The conformational changes of protein secondary structure in the presence of Zn(II) complexes were proven using UV–Vis absorption and circular dichroism techniques. Also, docking results confirmed the spectroscopic results. [ABSTRACT FROM AUTHOR]

A family of organonickel complexes has been prepared, fully characterized, and tested for their antiproliferative activity against estrogen-responsive human breast cancer cells (MCF7). The three SCS-type pincer ligands HL1, HL2, and HL3 and their corresponding Ni(ii) complexes NiL1, NiL2, and NiL3 have been synthesized and fully characterized, including by single crystal diffraction studies for the complexes. The complexes possess square planar geometry with two symmetrical 5-membered nickellacycles. Fluorescence spectroscopy, circular dichroism measurements, molecular modeling, colorimetric based assay and tumor transplantation studies were used to evaluate the protein binding and antiproliferative activities of these organometallic complexes both in vitro and in vivo. Fluorescence quenching was used to investigate bovine serum albumin (BSA) interaction at different temperatures (293, 303 and 313 K), and the results were analyzed using the classical Stern–Volmer equation, allowing us to propose a dynamic quenching mechanism. Studies in vitro on the antiproliferative activity of the three organonickel complexes against estrogen-responsive human breast cancer cells (MCF7) showed promising antitumor activity for NiL1 containing pyrrolidine fragments. In vivo administration of this compound significantly inhibits tumor growth in estrogen-dependent MC4L2 cancer cells in female BALB/c mice. [ABSTRACT FROM AUTHOR]

The interaction of La2 O2 CO3 nanoparticles (La NPs) with human serum albumin (HSA) has been studied. Analysis of the fluorescence quenching data of HSA using Stern–Volmer method showed that La NPs quenched HSA fluorescence in static quenching mode. Thermodynamic analysis indicated that hydrogen bonds and Van der Waals interactions play a major role for HSA–La NPs associations. Fluorescent displacement measurements confirmed that the primary binding site of La NPs was mainly located within site I (subdomain IIA) of HSA. The binding distance was calculated by using Forster resonance energy transfer theory. Also, the results of Fourier‐transform infrared spectroscopy, circular dichroism, three‐dimensional fluorescence and UV–visible measurements indicated that the binding of above La NPs to HSA may induce conformational and micro‐environmental changes of protein. This study suggested that the conformational change of HSA was at secondary structure of it and the biological activity of this protein was changed in the present of La NPs. [ABSTRACT FROM AUTHOR]

The C–H activation of methyl red (MR) (MR = 2-{[4-(dimethylamino)phenyl]diazenyl}benzoic acid) was achieved by reaction with Pd(OAc)2 under mild conditions. Metalation occurred at the ortho-position of the (dimethylamino)phenyl group in methyl red and the cyclometalated CNO pincer complex was obtained in good yield. The molecular structure shows that MR forms 6,5-fused chelate rings at the Pd(ii) center. Interaction of the pincer complex with human serum albumin (HSA) has been studied by fluorescence spectroscopy and circular dichroism. Fluorescence quenching at different temperatures was analyzed using the classical Stern–Volmer equation, and a dynamic quenching mechanism was proposed. Energy resonance transfer between HSA and 1a′ was examined according to Förster's non-radiative energy transfer theory. A distance of about 5.06 Å between the complex and Trp214 (HSA) was obtained. Docking studies showed that the binding pocket of subdomain IIA of HSA is the preferable pincer complex binding site. [ABSTRACT FROM AUTHOR]