Indirect co-culture of islet cells in 3D biocompatible collagen/laminin scaffold with angiomiRs transfected mesenchymal stem cells.

Diabetes is an autoimmune disease in which the pancreatic islets produce insufficient insulin. One of the treatment strategies is islet isolation, which may damage these cells as they lack vasculature. Biocompatible scaffolds are one of the efficient techniques for dealing with this issue. The current study is aimed to determine the effect of transfected BM-MSCS with angiomiR-126 and -210 on the survival and functionality of islets loaded into a 3D scaffold via laminin (LMN). AngiomiRs/Poly Ethylenimine polyplexes were transfected into bone marrow-mesenchymal stem cells (BM-MSCs), followed by 3-day indirect co-culturing with islets laden in collagen (Col)-based hydrogel scaffolds containing LMN. Islet proliferation and viability were significantly increased in LMN-containing scaffolds, particularly in the miRNA-126 treated group. Insulin gene expression was superior in Col scaffolds, especially, in the BM-MSCs/miRNA-126 treated group. VEGF was upregulated in the LMN-containing scaffolds in both miRNA-treated groups, specifically in the miRNA-210, leading to VEGF secretion. MiRNAs' target genes showed no downregulation in LMN-free scaffolds; while a drastic downregulation was seen in the LMN-containing scaffolds. The highest insulin secretion was recorded in the Oxidized dextran (Odex)/ColLMN+ group with miRNA-126. LMN-containing biocompatible scaffolds, once combined with angiomiRs and their downstream effectors, promote islets survival and restore function, leading to enhanced angiogenesis and glycemic status.

Sorafenib tosylate incorporation into mesoporous starch xerogel for in-situ micronization and oral bioavailability enhancement.

Poorly water-soluble drugs like sorafenib tosylate (SFB) can be made more soluble and orally bioavailable using a biocompatible hydrophilic matrix yields amorphous or microcrystalline drugs with high stability and low recrystallization risk. Mesoporous starch (MPS) due to its edibility, biodegradability, high surface area, and confined pores. In this study, MPS, either alone or in combination with polyvinylpyrrolidone (PVP), was employed for improving SFB oral bioavailability. To this aim, MPS was prepared in three steps: gelatinization, solvent exchange, and vacuum drying, after which it was used to incorporate SFB at various ratios using the immersion/solvent evaporation technique. Nitrogen adsorption/desorption analysis, Fourier transform infrared spectrometry (FTIR), field emission scanning electron microscopy (FE-SEM), powder X-ray diffraction (XRD) crystallography, and differential scanning calorimetry (DSC) were used to characterize SFB-loaded and drug-free samples, which confirmed the successful preparation of mesoporous structures with desirable uniform porosity, small pore size (about 5.3 nm), and specific surface area of about 24 m2/g. In-vitro dissolution testing revealed that the SFB dissolution rate increased substantially for the loaded MPS or MPS-PVP samples. Furthermore, when SFB was loaded in MPS-PVP, single-dose pharmacokinetics in rats confirmed an enhanced oral absorption kinetic. Therefore, impregnation of poorly soluble drugs such as SFB in the PVP-modified MPS excipient, which is constructed from a combination of mesoporous materials and a drug recrystallization inhibitor such as hydrophilic polymers, is proposed as a promising strategy for desirable enhancements in drug solubility, oral bioavailability, and efficacy.

Structural, mechanical, and biological characterization of hierarchical nanofibrous Fmoc-phenylalanine-valine hydrogels for 3D culture of differentiated and mesenchymal stem cells.

Fmoc-dipeptides are a class of short aromatic peptides featuring eminent supramolecular self-assembly, which is due to the aromaticity of the Fmoc group, which improves the association of peptide building blocks. This study aimed to introduce a new dipeptide hydrogel scaffold, Fmoc-phenylalanine-valine (Fmoc-FV), for 3D culture of various cells. Peptide hydrogel scaffolds were prepared by the pH-titration method in various concentrations and temperatures, and characterized by spectroscopic methods, including circular dichroism, attenuated total reflection FT-IR and fluorimetry. Mechanical behaviors such as thixotropy and temperature-sensitivity were investigated by oscillatory rheology. The Fmoc-FV hydrogels were then applied in 3D-culture of WJ-MSCs (mesenchymal stem cells), HUVECs (normal endothelial cells), and MDA-MB231 (tumor cell line) by live-dead fluorescence microscopy and Alamar blue viability assay experiments. The results confirmed that the ß-sheet structure is principally interlocked by π-π stacking of the Fmoc groups and entangled nanofibrous morphologies as revealed by FE-SEM. Fmoc-FV self-assembly in physiologic conditions resulted in a thermo-sensitive and shear-thinning hydrogel. Notably, the Fmoc-FV hydrogel exhibited cell type-dependent biological activity, so higher cell proliferation was attained in HUVEC or MDA-MB231 cells than WJ-MSCs, indicating a possible need for incorporating cell-adhesion ligands in the Fmoc-FV hydrogel matrix. Therefore, the structural and biological properties of the Fmoc-dipeptide hydrogels are inter-related and can affect their applications in 3D cell culture and regenerative medicine.

The Inflammatory and Fibrotic Patterns of Hepatic Stellate Cells Following Coagulation Factors (VII or X)-Shielded Adenovirus Infection.

The role of coagulation factors on the inflammatory effect of adenovirus (Ad) is an unresolved question that was considered herein. Adenovirus-36(Ad36) and adenovector-5-GFP(Ad5-GFP) were prepared; then, they were loaded with VII or FX factors. The size/charge parameters and transduction efficiency were evaluated using fluorescent microscopy and Zetasizer, respectively. The Ad36-coagulation factor complexes were added on the stellate cells, LX-2. Thereafter, the expression levels of inflammatory and fibrotic genes including PKR, IL-1ß, TNF-α, TIMP-1, collagen, and TGF-ß were measured by qPCR and ELISA assays. The loading of FVII or FX factors not only increased the size/charge of Ad5-GFP but also enhanced the transduction rate up to 60% and 75%, respectively, compared to the controls (45%). The PKR expression analysis showed an upregulation following treatment with all Ad36 forms (P = 0.0152). The IL-1ß and TNF-α cytokines analyses demonstrated that the Ad36-FVII complex elicited the highest inflammatory response (P = 0.05). Similarly, the fibrosis-related expression analysis revealed a more inductive role of FVII when loaded on Ad36, compared to the FX factor. The findings suggested that adenovirus elicited the innate inflammatory and activation state in the hepatic stellate cell. In addition, adenovirus shielded by FVII exhibited more innate inflammation as well as activation of the stellate cells than the FX-loaded virus.

Evaluation of the efficacy of albendazole sulfoxide (ABZ-SO)-loaded chitosan-PLGA nanoparticles in the treatment of cystic echinococcosis in laboratory mice.

Albendazole is known as the drug of choice for medical treatment of cystic echinococcosis (CE). Albendazole sulfoxide (ABZ-SO), as the main active metabolite of albendazole, has low efficacy in the disease due to low water solubility and poor absorptivity. PLGA nanoparticles (NPs) enhance the dissolution of poorly soluble drugs, and chitosan (CS) coating enhances oral drug delivery of NPs. In this study, the efficacy of ABZ-SO-loaded CS-PGLA NPs in the treatment of CE was evaluated in laboratory mice. ABZ-SO-loaded CS-PGLA NPs were prepared by nanoprecipitation and characterized by dynamic light scattering method and scanning electron microscopy. Thirty mice were intraperitoneally infected by 1000 protoscoleces of Echinococcus granulosus. Ten months later, the mice were allocated into 3 groups: groups 1 and 2 were treated with ABZ-SO and ABZ-SO-loaded CS-PGLA NPs, respectively, and the mice in group 3 remained untreated as the control group. The drugs were administered by gavage for 45 days at a daily dose of 10 mg/kg. Finally, all mice were opened and the cysts were collected, counted, weighed, and measured separately. The therapeutic effect of ABZ-SO in the number, weight, and volume of the cysts were not statistically significant compared with those in ABZ-SO-loaded CS-PGLA NPs and the control group. However, the therapeutic effect of ABZ-SO-loaded CS-PGLA NPs in the weight and volume of cysts were statistically significant when compared with that in the control group (p ˂ 0.05). In conclusions, this study revealed that ABZ-SO-loaded CS-PGLA NPs could enhance the therapeutic efficacy of ABZ-SO in the treatment of CE in laboratory mice.

The impact of different mutations at Arg54 on structure, chaperone-like activity and oligomerization state of human αA-crystallin: The pathomechanism underlying congenital cataract-causing mutations R54L, R54P and R54C.

A major part of cataractogenic mutations in human αA-Crystallin (αA-Cry) occurs at Arg residues. While Arg54 is highly conserved within different species, the cataractogenic mutations R54L, R54P and R54C have been recently identified in CRYAA gene, encoding human αA-Cry. The detailed structural and functional aspects, stability and amyloidogenic properties of αA-Cry were determined upon the above-mentioned missense mutations, using various spectroscopic techniques, gel electrophoresis, electron microscopy, size exclusion chromatography analyses, and chaperone-like activity assay. The different mutations at Arg54 result in diverse structural alterations among mutant proteins. In addition, the mutant proteins displayed reduced thermal stability, increased amyloidogenic properties and attenuated chaperone-like activity against aggregation of γ-Cry, catalase and lysozyme. The mutant proteins were also capable of forming larger oligomeric complexes with γ-Cry which is the natural partner of α-Cry in the eye lenses. The most significant structural and functional damages were observed upon R54L mutation which was also accompanied with increased oligomeric size distribution of the mutant protein. The cataractogenic nature of R54P mutation can be explained with its detrimental effect on chaperone-like activity, conformational stability and proteolytic digestibility of the mutant protein. Also, R54C αA-Cry displayed an important intrinsic propensity for disulfide protein cross-linking with significantly reduced chaperone-like activity against all client proteins. These mutations revealed a range of detrimental effects on the structure, stability and functional properties of αA-Cry which all together can explain the pathomechanisms underlying development of the associated congenital cataract disorders.

Physicochemical and biological characteristics of the nanostructured polysaccharide-iron hydrogel produced by microorganism Klebsiella oxytoca.

There is an increasing interest in the nanostructured polysaccharide-iron hydrogel produced by Klebsiella oxytoca. Critical physicochemical and biological characteristics of these nanostructures should be revealed for biomedical applications. Accordingly, an iron reducing strain K. oxytoca, which synthesizes biogenic polysaccharide-iron hydrogel nanoparticles, known as Fe (III)-exopolysaccharide (Fe-EPS) was isolated from a mineral spring. For microbiological identification purpose 16S rRNA sequence analysis and different morphological, physiological, and biochemical characteristics of the isolate were studied. Critical physicochemical and biological characteristics of the produced Fe-EPS were evaluated using transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy, X-ray crystallography (XRD), vibrating sample magnetometer (VSM). In addition, for the first time, Fe-EPS which synthesized by K. oxytoca was evaluated by dynamic light scattering (DLS), thermo gravimetric analysis (TGA), and cytotoxicity assay. TEM micrographs showed that the biogenic Fe-EPS is composed of ultra-small (about 1.8 nm) iron oxide nanoparticles (IONs) which are trapped in a polysaccharide matrix. The matrix was about 17% (w/w) of Fe-EPS total weight and provided a large negative charge of -71 mV. Interestingly, Fe-EPS showed a growth promotion effect on hepatocarcinoma cell line (Hep-G2) and 36% increase in the percentage of viability was observed by 24 h exposure to 500 µg ml-1 Fe-EPS.

Effect of lipid composition on incorporation of trastuzumab-PEG-lipid into nanoliposomes by post-insertion method: physicochemical and cellular characterization.

CONTEXT: Anti-HER2 immunoliposomes are promising nanotechnology based systems for active targeting of breast tumors, which depends on the amount of incorporated antibody. OBJECTIVE/AIM: In this work, we investigated the possible effect of lipid composition on the incorporation of trastuzumab-PEG-PE micelles into nanoliposomes and on their subsequent specific cellular targeting. MATERIALS AND METHODS: Trastuzumab (anti-HER2 monoclonal antibody) was monothiolated and conjugated to maleimide-PEG-PE micelles. Liposomes of different lipid compositions were prepared by the thin layer hydration. Trastuzumab-PEG-PE micelles were incorporated into the liposomes by the post-insertion method. The percentage of lipid mixing was determined based on fluorescence resonance energy transfer. Cellular binding and uptake of rhodamine-labeled immunoliposomes were studied in SKBR-3 (HER2(+++)) and MCF-7 (HER2(+)) cells. Also, antitumor cell activity of the immunoliposomes was compared to free trastuzumab and the liposomes. RESULTS: The lipid mixing of trastuzumab-PEG-PE micelles depended on the liposome composition. The immunoliposomes containing DPPC, cholesterol and PEG-PE showed prominent lipid mixing. The lipid mixing was consistent with the cell binding results which showed an efficient and specific binding of the immunoliposomes to SKBR-3 cells. Antitumor cell activity of the immunoliposomes in SKBR-3, unlike MCF-7 cells, depended on the content of trastuzumab. DISCUSSION: Cholesterol and PEG-PE in the liposome composition are prerequisites for a successful lipid mixing due to their ability to facilitate fusion. The higher lipid mixing results in higher antibody incorporation and consequently higher targeted cell binding. CONCLUSIONS: The lipid mixing depends on the liposome composition, which reflects targeted cell binding of the immunoliposomes.

Microencapsulation of (deoxythymidine)20-DOTAP complexes in stealth liposomes optimized by Taguchi design.

Stealth liposomes encapsulating oligonucleotides are considered as promising non-viral gene delivery carriers; however, general preparation procedures are not capable to encapsulate nucleic acids (NAs) efficiently. In this study, the lyophobic complexes of deoxythymidine20 oligonucleotide (dT20) and DOTAP were used instead of free dT20 for nano-encapsulation process by reverse phase evaporation method. Regarding the various factors that can potentially affect the liposome characteristics, Taguchi design was applied to analyze the simultaneous effects of factors comprising PEG-lipid (%), dT20/total lipid molar ratio, cholesterol (Chol%) and organic-to-aqueous phase ratio (o/w) at three levels. The response variables, hydrodynamic diameter, loading efficiency (LE%) and capacity (LC%), were studied by dynamic light scattering and ethidium bromide exclusion assay, respectively. The optimum condition described by minimum particle size as well as high LE% and LC% was obtained at 5% PEG-lipid, dT20/total lipid of 7, 20% Chol and o/w of 3 with an average size of 84 nm, LE% = 83.4% and LC% = 11.6%. Moreover, stability assessments in presence of heparin sulfate revealed the noticeable resistance, unlike DOTAP/dT20 lipoplexes, to premature release of NA. Transmission electron microscopy confirmed formation of discrete and circular vesicles encapsulating dT20.

Erythrocyte membrane-camouflaged mesoporous silica composite nanoparticles for loading and controlled release of the hepatoprotective agent silibinin: A-synthesis and physicochemical characterization.

OBJECTIVES: Milk thistle has long been used in the treatment of liver and biliary disorders. In the present study, to make a long-acting delivery system for silibinin (SBN, a major active constituent of milk thistle seeds with antioxidant and hepatoprotective function), mesoporous silica composite nanoparticles (NC) were synthesized and coated with RBC membrane. METHODS: A modified Stöber method was used for NC synthesis, which was then characterized using FE-SEM, DLS, TEM, FTIR, and EDAX techniques. A suitable lysis buffer was used to prepare RBC-ghost, and sonication was used to coat SBN-loaded NC (SBN-NC). The RBC-ghost coated SBN-NC (SBN-NC-RBCG) was evaluated by SDS-PAGE, Bradford, TEM, EDAX, and DLS methods. SBN release was then compared for the SBN-NC and SBN-NC-RBCG samples. KEY FINDINGS: the RBC membrane proteins were recovered from the coating of SBN-NC-RBCG, and SBN release was sustained over 24 h when compared with the SBN-NC. CONCLUSIONS: Overall, through prolonging circulation in the bloodstream and evading the immune system, the developed system can improve SBN bioavailability in liver inflammation and fibrosis conditions that need further research.

Gold nanostructures in melanoma: Advances in treatment, diagnosis, and theranostic applications.

Melanoma, a lethal form of skin cancer, poses a significant challenge in oncology due to its aggressive nature and high mortality rates. Gold nanostructures, including gold nanoparticles (GNPs), offer myriad opportunities in melanoma therapy and imaging due to their facile synthesis and functionalization, robust stability, tunable physicochemical and optical properties, and biocompatibility. This review explores the emerging role of gold nanostructures and their composites in revolutionizing melanoma treatment paradigms, bridging the gap between nanotechnology and clinical oncology, and offering insights for researchers, clinicians, and stakeholders. It begins by elucidating the potential of nanotechnology-driven approaches in cancer therapy, highlighting the unique physicochemical properties and versatility of GNPs in biomedical applications. Various therapeutic modalities, including photothermal therapy, photodynamic therapy, targeted drug delivery, gene delivery, and nanovaccines, are discussed in detail, along with insights from ongoing clinical trials. In addition, the utility of GNPs in melanoma imaging and theranostics is explored, showcasing their potential in diagnosis, treatment monitoring, and personalized medicine. Furthermore, safety considerations and potential toxicities associated with GNPs are addressed, underscoring the importance of comprehensive risk assessment in clinical translation. Finally, the review concludes by discussing current challenges and future directions, emphasizing the need for innovative strategies to maximize the clinical impact of GNPs in melanoma therapy.

Expanding horizons in cancer therapy by immunoconjugates targeting tumor microenvironments.

Immunoconjugates are promising molecules combining antibodies with different agents, such as toxins, drugs, radionuclides, or cytokines that primarily aim to target tumor cells. However, tumor microenvironment (TME), which comprises a complex network of various cells and molecular cues guiding tumor growth and progression, remains a major challenge for effective cancer therapy. Our review underscores the pivotal role of TME in cancer therapy with immunoconjugates, examining the intricate interactions with TME and recent advancements in TME-targeted immunoconjugates. We explore strategies for targeting TME components, utilizing diverse antibodies such as neutralizing, immunomodulatory, immune checkpoint inhibitors, immunostimulatory, and bispecific antibodies. Additionally, we discuss different immunoconjugates, elucidating their mechanisms of action, advantages, limitations, and applications in cancer immunotherapy. Furthermore, we highlight emerging technologies enhancing the safety and efficacy of immunoconjugates, such as antibody engineering, combination therapies, and nanotechnology. Finally, we summarize current advancements, perspectives, and future developments of TME-targeted immunoconjugates.

Harnessing the Potential of Self-Assembled Peptide Hydrogels for Neural Regeneration and Tissue Engineering.

Spinal cord injury, traumatic brain injury, and neurosurgery procedures usually lead to neural tissue damage. Self-assembled peptide (SAP) hydrogels, a type of innovative hierarchical nanofiber-forming peptide sequences serving as hydrogelators, have emerged as a promising solution for repairing tissue defects and promoting neural tissue regeneration. SAPs possess numerous features, such as adaptable morphologies, biocompatibility, injectability, tunable mechanical stability, and mimicking of the native extracellular matrix. This review explores the capacity of neural cell regeneration and examines the critical aspects of SAPs in neuroregeneration, including their biochemical composition, topology, mechanical behavior, conductivity, and degradability. Additionally, it delves into the latest strategies involving SAPs for central or peripheral neural tissue engineering. Finally, the prospects of SAP hydrogel design and development in the realm of neuroregeneration are discussed.

Hypoxia-preconditioned WJ-MSC spheroid-derived exosomes delivering miR-210 for renal cell restoration in hypoxia-reoxygenation injury.

BACKGROUND: Recent advancements in mesenchymal stem cell (MSC) technology have paved the way for innovative treatment options for various diseases. These stem cells play a crucial role in tissue regeneration and repair, releasing local anti-inflammatory and healing signals. However, challenges such as homing issues and tumorigenicity have led to exploring MSC-exosomes as a promising alternative. MSC-exosomes have shown therapeutic potential in conditions like renal ischemia-reperfusion injury, but low production yields hinder their clinical use. METHODS: To address this limitation, we examined hypoxic preconditioning of Wharton jelly-derived MSCs (WJ-MSCs) 3D-cultured in spheroids on isolated exosome yields and miR-21 expression. We then evaluated their capacity to load miR-210 into HEK-293 cells and mitigate ROS production, consequently enhancing their survival and migration under hypoxia-reoxygenation conditions. RESULTS: MiR-210 overexpression was significantly induced by optimized culture and preconditioning conditions, which also improved the production yield of exosomes from grown MSCs. The exosomes enriched with miR-210 demonstrated a protective effect by improving survival, reducing apoptosis and ROS accumulation in damaged renal cells, and ultimately promoting cell migration. CONCLUSION: The present study underscores the possibility of employing advanced techniques to maximize the therapeutic attributes of exosomes produced from WJ-MSC spheroid for improved recovery outcomes in ischemia-reperfusion injuries.

Targeted drug delivery to the thrombus by fusing streptokinase with a fibrin-binding peptide (CREKA): an in silico study.

Aim: Streptokinase has poor selectivity and provokes the immune response. In this study, we used in silico studies to design a fusion protein to achieve targeted delivery to the thrombus. Materials & methods: Streptokinase was analyzed computationally for mapping. The fusion protein modeling and quality assessment were carried out on several servers. The enzymatic activity and the stability of the fusion protein and its complex with plasminogen were assessed through molecular docking analysis and molecular dynamics simulation respectively. Results: Physicochemical properties analysis, protein quality assessments, protein-protein docking and molecular dynamics simulations predicted that the designed fusion protein is functionally active. Conclusion: Our results showed that this fusion protein might be a prospective candidate as a novel thrombolytic agent with better selectivity.

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Improving cellular uptake and in vivo tumor suppression efficacy of liposomal oligonucleotides by urea as a chemical penetration enhancer.

BACKGROUND: Liposomes are among the most widely used carriers for the delivery of antisense oligonucleotides (AsODNs) to intracellular targets. Although different strategies have been employed, the question of how to improve liposomal uptake and enhance the release of AsODN into cytoplasm still remains to be answered with respect to the use of a safe, easy and economic method. In the present study, the possibility of enhancing such processes at cellular and animal levels using urea as a penetration enhancer was investigated. METHODS: To perform this investigation, a cationic liposome containing an AsODN against protein kinase (PKC)-α was prepared, and the effect of urea on its cellular internalization and the related sequence-specific inhibition of gene expression in human lung adenocarcinoma A549 cells were investigated by flow cytometry and the reverse transcriptase-polymerase chain reaction, respectively. In in vivo studies, a xenograft lung tumor was established in nude mice by A549 cells and the enhancement effect of urea toward the effects of liposomal AsODN on tumor growth was investigated. RESULTS: Cellular studies revealed that urea treatment increases liposomal uptake and the release of AsODN into the cytoplasm by approximately 40%. Sequence-specific inhibition of target gene PKC-α expression was also increased by approximately two-fold by urea at 200-300 nM AsODN. In animal studies, urea significantly decreased the tumor volume (approximately 40%) and increased its doubling time from approximately 13 days to 17 days. CONCLUSIONS: Urea, and possibly other membrane fluidizers, could be regarded as penetration enhancers for liposomal AsODN delivery and may improve the therapeutic effect of these gene-therapy vectors at both cellular and animal levels.

Rheological Characteristics of Soluble Cress Seed Mucilage and ß-Lactoglobulin Complexes with Salts Addition: Rheological Evidence of Structural Rearrangement.

Functional, physicochemical, and rheological properties of protein-polysaccharide complexes are remarkably under the influence of the quality of solvent or cosolute in a food system. Here, a comprehensive description of the rheological properties and microstructural peculiarities of cress seed mucilage (CSM)-ß-lactoglobulin (Blg) complexes are discussed in the presence of CaCl2 (2-10 mM), (CSM-Blg-Ca), and NaCl (10-100 mM) (CSM-Blg-Na). Our results on steady-flow and oscillatory measurements indicated that shear thinning properties can be fitted well by the Herschel-Bulkley model and by the formation of highly interconnected gel structures in the complexes, respectively. Analyzing the rheological and structural features simultaneously led to an understanding that formations of extra junctions and the rearrangement of the particles in the CSM-Blg-Ca could enhance elasticity and viscosity, as compared with the effect of CSM-Blg complex without salts. NaCl reduced the viscosity and dynamic rheological properties and intrinsic viscosity through the salt screening effect and dissociation of structure. Moreover, the compatibility and homogeneity of complexes were approved by dynamic rheometry based on the Cole-Cole plot supported by intrinsic viscosity and molecular parameters such as stiffness. The results outlined the importance of rheological properties as criteria for investigations that determine the strength of interaction while facilitating the fabrication of new structures in salt-containing foods that incorporate protein-polysaccharide complexes.

Exploring the Effects of Various Capping Agents on Zinc Sulfide Quantum Dot Characteristics and In-vitro Fate.

The choice of capping agents used during the synthesis process of quantum dots (QDs) can significantly influence their fate and fundamental properties. Hence, choosing an appropriate capping agent is a critical step in both synthesis and biomedical application of QDs. In this research, ZnS QDs were synthesized via chemical precipitation process and three commonly employed capping agents, namely mercaptoethanol (ME), mercaptoacetic acid (MAA), and cysteamine (CA), were used to stabilize the QDs. This study was aimed to examine how these capping agents impact the physicochemical and optical characteristics of ZnS QDs, as well as their interactions with biological systems. The findings revealed that the capping agents had considerable effects on the behavior and properties of ZnS QDs. MAA-QD exhibited superior crystal lattice, smaller size, and significant quantum yield (QY). In contrast, CA-QDs demonstrated the lowest QY and the highest tendency for aggregation. ME-QDs exhibited intermediate characteristics, along with an acceptable level of cytotoxicity, rapid uptake by cells, and efficient escape from lysosomes. Consequently, it is advisable to select capping agents in accordance with the specific objectives of the research.

Biocompatible scaffolds based on collagen and oxidized dextran for endothelial cell survival and function in tissue engineering.

Angiogenesis is a vital step in tissue regeneration. Hence, the current study aimed to prepare oxidized dextran (Odex)/collagen (Col)-hydrogels with laminin (LMN), as an angiogenic extracellular matrix (ECM) component, for promoting human umbilical vein endothelial cell (HUVEC) proliferation and function. Odex/Col scaffolds were constructed at various concentrations and temperatures. Using oscillatory rheometry, scanning electron microscopy (SEM), and cell viability testing, the scaffolds were characterized, and then HUVEC proliferation and function was compared with or without LMN. The gelation time could be modified by altering the Odex/Col mass ratio as well as the temperature. SEM showed that Odex/Col hydrogels had a more regular three-dimensional (3D) porous structure than the Col hydrogels. Moreover, HUVECs grew faster in the Col scaffold (12 mg/mL), whereas the Odex (30 mg/mL)/Col (6 mg/mL) scaffold exhibited the lowest apoptosis index. Furthermore, the expression level of vascular endothelial growth factor (VEGF) mRNA in the group without LMN was higher than that with LMN, and the Odex (30 mg/mL)/Col (6 mg/mL) scaffold without LMN had the highest VEGF protein secretion, allowing the cells to survive and function effectively. Odex/Col scaffolds, with or without LMN, are proposed as a tissue engineering construct to improve HUVEC survival and function for angiogenesis.

L-asparaginase immobilization in supramolecular nanogels of PEG-grafted poly HPMA and bis(α-cyclodextrin) to enhance pharmacokinetics and lower enzyme antigenicity.

L-asparaginase (ASNase) enzyme has limited therapeutic use due to its poor pharmacokinetics and immunogenicity. To overcome these obstacles, we immobilized ASNase in biocompatible poly hydroxypropyl methacrylamide (P(HPMA))-based nanogels simply formed through the host-guest inclusion complex of ASNase-conjugated random copolymer of HPMA and polyethylene glycol (PEG) acrylate (P(HPMA-MPEGA)) and α-cyclodextrin dimer (bisCD) using cystamine as a linker. The effects of bisCD and polymer concentrations on particle size, gelation time, and recovery of enzyme activity were investigated. The ASNase-conjugated bisCD nanogels were discrete, homogeneous, and spherical with a mean projected diameter of 148 ± 41 nm. ASNase immobilized in the bisCD nanogels caused cytotoxicity on HL-60 cell line with IC50 of 3 IU/ml. In-vivo rat study revealed that the immobilized ASNase reduced the enzyme antigenicity and resulted in 8.1 folds longer circulation half-life than the native enzyme. Conclusively, immobilization of ASNase in P(HPMA-MPEGA) and bisCD supramolecular nanogels could enhance the therapeutic value of ASNase in cancer chemotherapy.