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The simulated liposome models provide events in molecular biological science and cellular biology. These models may help to understand the cell membrane mechanisms, biological cell interactions, and drug delivery systems. In addition, the liposomes model may resolve specific issues such as membrane transports, ion channels, drug penetration in the membrane, vesicle formation, membrane fusion, and membrane protein function mechanism. One of the approaches to investigate the lipid membranes and the mechanism of their formation is by molecular dynamics (MD) simulations. In this study, we used the coarse-grained MD simulation approach and designed a liposome model system. To simulate the liposome model, we used phospholipids that are present in the structure of natural cell membranes (1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE)). Simulation conditions such as temperature, ions, water, lipid concentration were performed based on experimental conditions. Our results showed a liposome model (ellipse vesicle structure) during the 2100 ns was formed. Moreover, the analysis confirmed that the stretched and ellipse structure is the best structure that could be formed. The eukaryotic and even the bacterial cells have elliptical and flexible structures. Usually, an elliptical structure is more stable than other assembled structures. The results indicated the assembly of the lipids is directed through short-range interactions (electrostatic interactions and, van der Waals interactions). Total energy (Van der Waals and electrostatic interaction energy) confirmed the designed elliptical liposome structure has suitable stability at the end of the simulation process. Our findings confirmed that phospholipids DOPC and DOPE have a good tendency to form bilayer membranes (liposomal structure) based on their geometric shapes and chemical-physical properties. Finally, we expected the simulated liposomal structure as a simple model to be useful in understanding the function and structure of biological cell membranes. Furthermore, it is useful to design optimal, suitable, and biocompatible liposomes as potential drug carriers., (© 2022. The Author(s).)

Sulforaphane (SF) was loaded into the multi-functioned rattle-structured gold nanorod mesoporous silica nanoparticles core-shell to improve its stability and efficacy through its efficient delivery to tumors. The rattle-structured gold nanorod mesoporous silica nanoparticles (rattle-structured AuNR@mSiO 2 core-shell NPs) were obtained by covering the surface of Au NPs with Ag and mSiO 2 shell and subsequently selective Ag shell etching strategy. Then the surface of rattle-structured AuNR@mSiO 2 NPs was decorated with thiolated polyethylene glycol-FITC and thiolated polyethylene glycol-folic acid to the designed form. The obtained FITC/FA@ [rattle-structured AuNR@mSiO 2 ] NPs was characterized by different techniques including energy dispersive X-ray spectroscopy (EDX), scanning and transmission electron microscopy (SEM & TEM), UV-visible spectrophotometer and dynamic light scattering (DLS). The FITC/FA@ [rattle-structured AuNR@mSiO 2 ] NPs has an average diameter around ~33 nm, which increases to ~38 nm after the loading of sulforaphane. The amount of the loaded drug was ~ 2.8×10-4 mol of SF per gram of FITC/FA@ [rattle-structured AuNR@mSiO 2 ] NPs. The rattle-structured AuNR@mSiO 2 and FITC/FA@ [rattle-structured AuNR@mSiO 2 ] NPs showed little inherent cytotoxicity, whereas the SF loaded FITC/FA@ [rattle-structured AuNR@mSiO 2 ] NPs was highly cytotoxic in the case of MCF-7 cell line. Finally, Fluorescence microscopy and flow cytometry were used to demonstrate that the nanoparticles could be accumulated in specific regions and SF loaded FITC/FA@ [Fe 3 O 4 @Au] NPs efficiently induce apoptosis in MCF-7 cell line Graphical Abstract., Competing Interests: The authors report no declarations of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Efficient delivery of anticancer chemotherapies such as paclitaxel (PTX) can improve treatment strategy in a variety of tumors such as breast and ovarian cancers. Accordingly, researches on polymeric nanomicelles continue to find suitable delivery systems. However, due to biocompatibility concerns, a few micellar nanoformulations have exquisitely been translated into clinical uses. Here, we report the synthesis of novel water-soluble nanomicelles using bioactive polyurethane (PU) polymer and efficient delivery of PTX in the human breast cancer MCF-7 cells., Results: The amphiphilic polyurethane was prepared through formation of urethane bounds between hydroxyl groups in poly (tetramethylene ether) glycol (PTMEG) and dimethylol propionic acid with isocyanate groups in toluene diisocyanate (TDI). The free isocyanate groups were blocked with phenol, while the free carboxyl groups of dimethylol propionic acid were reacted with triethylamine to attain ionic centers in the polymer backbone. These hydrophobic PTMEG blocks displayed self-assembly forming polymeric nanomicelles in water. The PTX loaded PU nanomicelles showed suitable physical stability, negative zeta potential charge (-43) and high loading efficiency (80%) with low level of critical micelle concentration (CMC). In vitro drug release profile showed a faster rate of drug liberation at pH 5.4 as compared to that of pH 7.4, implying involvement of a pH-sensitive mechanism for drug release from the nanomicelles. The kinetic of release exquisitely obeyed the Higuchi model, confirming involvement of diffusion and somewhat erosion at pH 5.4. These nanomicelles significantly inhibited the growth and proliferation of the human breast cancer MCF-7 cells, leading them to apoptosis. The real time RT-PCR analysis confirmed the activation of apoptosis as result of liberation of cytochrome c in the cells treated with the PTX loaded PU nanomicelles. The comet assay analysis showed somewhat DNA fragmentation in the treated cells., Conclusions: Based upon these findings, we propose that the bioactive waterborne polyurethane nanomicelles can be used as an effective nanocarrier for delivery of anticancer chemotherapies such as paclitaxel., (© 2012 Khosroushahi et al; licensee BioMed Central Ltd.)

A novel design of gold-coated iron oxide nanoparticles was fabricated as a potential delivery system to improve the efficiency and stability of d, l-sulforaphane as an anticancer drug. To this purpose, the surface of gold-coated iron oxide nanoparticles was modified for sulforaphane delivery via furnishing its surface with thiolated polyethylene glycol-folic acid and thiolated polyethylene glycol-FITC. The synthesized nanoparticles were characterized by different techniques such as FTIR, energy dispersive X-ray spectroscopy, UV-visible spectroscopy, scanning and transmission electron microscopy. The average diameters of the synthesized nanoparticles before and after sulforaphane loading were obtained ∼ 33 nm and ∼ 38 nm, respectively, when ∼ 2.8 mmol/g of sulforaphane was loaded. The result of cell viability assay which was confirmed by apoptosis assay on the human breast cancer cells (MCF-7 line) as a model of in vitro-cancerous cells, proved that the bare nanoparticles showed little inherent cytotoxicity, whereas the sulforaphane-loaded nanoparticles were cytotoxic. The expression rate of the anti-apoptotic genes (bcl-2 and bcl-xL), and the pro-apoptotic genes (bax and bak) were quantified, and it was found that the expression rate of bcl-2 and bcl-xL genes significantly were decreased when MCF-7 cells were incubated by sulforaphane-loaded nanoparticles. The sulforaphane-loaded into the designed gold-coated iron oxide nanoparticles, acceptably induced apoptosis in MCF-7 cells. [ABSTRACT FROM AUTHOR]

Natural polymers and proteins such as chitosan (CS) and albumin (Alb) have recently attracted much attention both in drug delivery and gene delivery. The underlying rationale is their unique properties such as biodegradability, biocompatibility and controlled release. This study aimed to prepare novel albumin-chitosan-DNA (Alb-CS-DNA) core-shell nanoparticles as a plasmid delivery system and find the best conditions for their preparation. Phase separation method and ionic interaction were used for preparation of Alb nanoparticles and Alb-CS-DNA core-shell nanoparticles, respectively. The effects of three important independent variables (1) CS/Alb mass ratio, (2) the ratios of moles of the amine groups of cationic polymers to those of the phosphate groups of DNA (N/P ratio), and (3) Alb concentration, on the nanoparticle size and loading efficiency of the plasmid were investigated and optimized through Box-Behnken design of response surface methodology (RSM). The optimum conditions were found to be CS/Alb mass ratio = 3, N/P ratio = 8.24 and Alb concentration = 0.1 mg/mL. The most critical factors for the size of nanoparticles and loading efficiency were Alb concentration and N/P ratio. The optimized nanoparticles had an average size of 176 ± 3.4 nm and loading efficiency of 80 ± 3.9 %. Cytotoxicity experiments demonstrated that the prepared nanoparticles were not toxic. The high cellular uptake of nanoparticles (~85 %) was shown by flow cytometry and fluorescent microscopy. [ABSTRACT FROM AUTHOR]

Chitosan (CHS) and chitin (CHT) biopolymers have found many applications in the field of controlled-release drug delivery systems. Herein, molecular dynamics (MD) simulation and binding free energy calculations were used to investigate the potentials of CHS and CHT polymers for the controlled release of follicle-stimulating hormone (FSH). The results indicated that FSH conformation did not change in the presence of CHS and CHT. In addition, FSH-polymer interactions caused stability of the 3 10 -helix structure of the alpha subunits of FSH (FSHα). Both the biopolymers interacted with the protein mainly through the hydrophobic forces. CHS has more affinity for FSH when compared with CHT. Furthermore, in both systems, the affinity of polymers for FSHα was more than that for beta subunits of FSH (FSHβ). The results suggested that the polysaccharides might improve the controlled-release FSH delivery. [ABSTRACT FROM AUTHOR]

Cationic chitosan, a naturally degradable and biocompatible polysaccharide, has shown considerable promise as a drug delivery system. However, its limited solubility in water at neutral and alkaline pH has restricted its broader application. To overcome this challenge, various chemical modification strategies have been explored to enhance the solubility of chitosan. One such strategy involves the development of chitosan-deoxycholic acid-polyacrylic acid (CDP) copolymers, which are novel amphiphilic derivatives of chitosan that exhibit excellent water solubility and self-assembly properties. Herein, we investigated the potential of CDP as an anionic carrier for two model proteins: the positively charged Lysozyme and the negatively charged Pyrazinamidase. The objective of this investigation is to elucidate the role of electrostatic interactions between the copolymer and the proteins during the drug encapsulation process. A combined approach utilizing experimental techniques and molecular dynamics (MD) simulations was used to investigate the interactions between the polymer and the proteins, as well as any potential structural changes to the proteins. The results suggest contrasting binding mechanisms for the two proteins: Lysozyme being entrapped within the cationic polymer network and Pyrazinamidase being adsorbed onto the surface of the polymeric assemblies. Binding energy calculations revealed favorable physical interactions between CDP and Lysozyme, while Pyrazinamidase exhibited unfavorable binding. These findings demonstrated that CDP may serve as a promising carrier for positively charged drugs due to its favorable interactions and potential entrapment within the polymer network. The favorable interactions observed between CDP and Lysozyme suggest that CDP could be further explored as a delivery system for positively charged therapeutic proteins. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • A new strategy was developed to deliver 5-ASA to an inflamed site in the colon by HbNPs. • This conjugated drug is protected against chemical and enzymatic hydrolysis. • Higher cellular uptake and prolonged release time for 5-ASA-HbNPs in the Caco-2 cells. • HbNPs increase the effectiveness of drug therapy due to adhesion to intestinal epithelial cells. • In vivo imaging of mouse colon shows the localization of drug in the descending colon. A colonic drug delivery system was developed to specifically deliver 5-aminosalicylic acid (5-ASA) to the inflamed site by conjugating with hemoglobin nanoparticles (HbNPs). The 5-ASA-HbNPs (eight 5-ASA molecules per Hb molecule) with the size of 220 nm and zeta potential of −14.6 mV is a tailored nanoparticle able to pass through the mucus layer. The 5-ASA-HbNPs do not undergo chemical and enzymatic hydrolysis in the simulated gastrointestinal fluids over 6 h. Significantly higher cellular uptakes and prolonged release was seen for the 5-ASA-HbNPs in Caco-2 cells, compared to free 5-ASA over 72 h. In addition, 5-ASA-HbNPs revealed similar therapeutic effectiveness with free 5-ASA against tumor necrosis factor and showed less inhibitory concentration (IC50) for myeloperoxidase enzyme activity. In vivo imaging of mouse demonstrated the localization of drug in the descending colon after oral administration and about 15% of the administered dose was recovered as 5-ASA from urine in 6 h. The use of these nanoparticles with the mucus adhesion properties and permeability to intestinal epithelial cells can be a good candidate with potential application in the colonic drug delivery field. [ABSTRACT FROM AUTHOR]

Graphene quantum dots (GQDs) represent a new generation of graphene-based nanomaterials with enormous potential for use and development of a variety of biomedical applications. However, up to now little studies have investigated the impact of GQDs on human health in case of exposure. GQDs were synthesized from citric acid as carbon precursor by hydrothermal treatment at 160 °C for 4 h. The synthesized GQDs showed strong blue emission under UV-Irradiation with fluorescence quantum yield of 9.8%. The obtained GQDs were further carbonized, activated and functionalized by nitric acid vapor method. Nitrogen adsorption/desorption isotherms were used to analyze the surface area and porous structures of GQDs. The results revealed that compared to GQDs, the specific surface area of functionalized graphene quantum dots (fGQDs) has been increased from 0.0667 to 2.5747 m2/g and pore structures have been enhanced significantly. The potential cytotoxic effect of GQDs, fGQDs and GO suspensions was evaluated on HFF cell line using MTT assays and flow cytometry method after 24 h incubation. We have for the first time demonstrated that by carbonization, activation and functionalization of GQDs they still showed cytocompatible properties. We observed excellent biocompatibility of GQDs and fGQDs at low concentrations. Moreover, the results suggested that modification of GQDs yields product suspensions with high surface area, enhanced pore volume and loading capacities. Thus, fGQDs represent an attractive candidate for further use in drug delivery systems and bio-imaging application. Novel modified graphene quantum dots prepared from natural, eco-friendly and biocompatible materials. Unlabelled Image • Blue luminescent graphene quantum dots were modified by acid vapor method. • The modified graphene quantum dots showed very high specific surface area with enhanced pore structures. • The functionalized graphene quantum dots revealed high loading capacities. • The excellent biocompatibility was confirmed toward HFF cells at low concentrations. [ABSTRACT FROM AUTHOR]