Niosomes containing paclitaxel and gold nanoparticles with different coating agents for efficient chemo/photothermal therapy of breast cancer.

Breast cancer (BC) is one of the most common cancers in women, and chemotherapy is usually used to overcome this cancer. To improve drug delivery to cancer sites and reduce their side effects, nanocarriers such as niosomes (NIOs) are used. Moreover, a combination of other therapeutic methods like photothermal therapy (PTT) can help to enhance the chemotherapy effect. The aim of this research is the design a nanocarrier that simultaneously delivers chemotherapy and PTT agents. To achieve this goal, NIOs containing paclitaxel (PTX) as a chemotherapeutic agent and spherical gold nanoparticles (AuNPs) coated with citrate, chitosan (CS), and polyamidoamine (PAMAM) as a PTT agent were synthesized by thin hydration methods. Their physicochemical properties were determined by dynamic light scattering, UV-Vis, Fourier-transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM) analysis. Cellular uptake, cell cytotoxicity, hyperthermia, and apoptosis effects of the proposed system were investigated in the MCF-7 BC cell line. The cellular uptake of NIOs/AuNPs-PAMAM (99.21%) and NIOs/AuNPs-CS (98.93%) by MCF-7 cells was higher than that of NIOs/AuNPs (79.55%), demonstrating that surface charge plays a key role in the cellular uptake of NPs. The MTT assay showed the cell viability of 45.48% for NIOs/AuNPs/PTX, 34.24% for NIOs/AuNPs-CS/PTX, and 37.67% for NIOs/AuNPs-PAMAM/PTX after 48 h of treatment. However, the application of hyperthermia significantly decreased the viability of cells treated with NIOs/AuNPs/PTX (37.72%), NIOs/AuNPs-CS/PTX (10.49%), and NIOs/AuNPs-PAMAM/PTX (4.1%) after 48 h. The apoptosis rate was high in NIOs/AuNPs-PAMAM/PTX (53.24%) and NIOs/AuNPs-CS/PTX (55.4%) confirming the data from MTT. In conclusion, the result revealed that combined PTT with chemotherapy increased cell cytotoxicity effects against the MCF-7 cells, and the AuNPs with various coating agents affected cellular uptake and hyperthermia which can be considered for efficient BC therapy.

Increased antibiofilm and growth inhibitory effect of Imipenem/Cilastatin nanoliposomes against clinical Pseudomonas aeruginosa isolates.

Numerous infections are linked to Pseudomonas aeruginosa. It is one of the major medical concerns because of virulence and antibiotic resistance. Antibiotic encapsulation in liposomes is a good strategy for controlling infections caused by this microorganism. Evaluation of anti-Pseudomonas aeruginosa effect of liposomal form of Imipenem/Cilastatin in vitro condition. By using the disk agar diffusion technique, the isolates' pattern of antibiotic resistance was identified. The antibiotic was placed into the nanoliposome after it had been made using the thin layer and ethanol injection techniques. SEM and DLS were used to determine the size, shape, and zeta potential of the encapsulated drug form and the empty nanoliposome. Additionally, Imipenem/Cilastatin encapsulation in nanoliposomes was studied using FT-IR spectroscopy. In the microbial assay experiments the MIC, MBC and MBEC of liposomal and free drug forms were determined. The nanoparticles were spherical, with a diameter ranging from 30 to 39 nm, and the EE% in the thin layer and ethanol injection procedures were 97 and 98, respectively. Imipenem/Cilastatin nanoliposomes showed peaks at 3009 cm-1 and 1650 cm-1, demonstrating the thermodynamic stability for the chemical structure of the drug enclosed and validating the encapsulation of antibiotic in the nanoliposomes. When compared to free drug forms, nanoliposomes had lower MIC and MBC values in the majority of the isolates and had a greater ability to eradicate the biofilm formation. It was shown that the two nanoliposome preparation techniques were more efficient in 80% of the isolates, which had outcomes that were consistent with those of numerous other investigations. Overall, we demonstrated that the antibacterial activity of nanoliposomes was higher than that of the free drug form based on the evaluation of their MIC and MBC. Pharmaceutical nanoliposome techniques provide an excellent future perspective on how to manage microbial infections that are resistant to antibiotics.

Effect of Silver Nanoparticles of Herbal Origin on the Compressive and Push-out Bond Strengths of Mineral Trioxide Aggregate.

Introduction: The purpose of this in vitro study was to investigate the effect of incorporating silver nanoparticles (AgNPs) of herbal origin into mineral trioxide aggregate (MTA) on the push-out bond strength (PBS) and compressive strength (CS) in simulated furcal area perforations. Materials and Methods: In this in vitro study, simulated furcal area perforations (1.3 mm in diameter and 2 mm in depth) were created in 40 extracted human lower molar teeth, which were divided into two groups (n=20): MTA alone and MTA combined with AgNPs (2% wt). Using a universal testing machine, PBS was evaluated by performing push-out tests, while CS was assessed using cylindrical specimens. The normal distribution of data was checked using the Kolmogorov-Smirnov test, and statistical analysis was performed using two-way ANOVA. Results: The CS results showed no significant difference between the MTA group at 4 and 21 days (P=0.297), but a significant difference was observed in the nanosilver/MTA group (P=0.013). However, there was no significant difference in the push-out bond strength among the study groups (P>0.05). Conclusion: The incorporation of herbal origin silver nanoparticles did not significantly affect the PBS or CS of MTA.

Electrosprayed Nanoparticles Containing Hydroalcoholic Extract of Echinacea purpurea (L.) Moench Stimulates Immune System by Increasing Inflammatory Factors in Male Wistar Rats.

Purpose: Echinacea purpurea (L.) Moench is a member of the Asteraceae family and is traditionally used mainly due to its immunostimulatory properties. Various compounds including alkylamides and chicoric acid were reported as active ingredients of E. purpurea. Here, we aimed to prepare electrosprayed nanoparticles (NPs) containing hydroalcoholic extract of E. purpurea using Eudragit RS100 (EP-Eudragit RS100 NPs) to improve the immunomodulatory effects of the extract. Methods: The EP-Eudragit RS100 NPs with the different extract:polymer ratios and solution concentrations were prepared using the electrospray technique. The size and morphology of the NPs were evaluated using dynamic light scattering (DLS) and field emission-scanning electron microscopy (FE-SEM). To evaluate the immune responses, male Wistar rats were administrated with the prepared EP-Eudragit RS100 NPs and plain extract in the final dose of 30 or 100 mg/kg. The blood samples of the animals were collected and the inflammatory factors and complete blood count (CBC) were investigated. Results: In vivo studies indicated that the plain extract and EP-Eudragit RS100 NPs (100 mg/kg) significantly increased the serum level of tumor necrosis factor-α (TNF-α) and interleukin 1-ß (IL1-ß) whereas the EP-Eudragit RS100 NPs (30 mg/kg) significantly increased the number of white blood cells (WBCs) compared to the control group. Lymphocytes' count in all groups was increased significantly compared to the control group (P<0.05) whereas other CBC parameters remained unchanged. Conclusion: The prepared EP-Eudragit RS100 NPs by electrospray technique caused significant reinforcement in the immunostimulatory effects of the extract of E. purpurea.

Biomaterial-based delivery platforms for transdermal immunotherapy.

Nowadays, immunotherapy is one of the most essential treatments for various diseases and a broad spectrum of disorders are assumed to be treated by altering the function of the immune system. For this reason, immunotherapy has attracted a great deal of attention and numerous studies on different approaches for immunotherapies have been investigated, using multiple biomaterials and carriers, from nanoparticles (NPs) to microneedles (MNs). In this review, the immunotherapy strategies, biomaterials, devices, and diseases supposed to be treated by immunotherapeutic strategies are reviewed. Several transdermal therapeutic methods, including semisolids, skin patches, chemical, and physical skin penetration enhancers, are discussed. MNs are the most frequent devices implemented in transdermal immunotherapy of cancers (e.g., melanoma, squamous cell carcinoma, cervical, and breast cancer), infectious (e.g., COVID-19), allergic and autoimmune disorders (e.g., Duchenne's muscular dystrophy and Pollinosis). The biomaterials used in transdermal immunotherapy vary in shape, size, and sensitivity to external stimuli (e.g., magnetic field, photo, redox, pH, thermal, and even multi-stimuli-responsive) were reported. Correspondingly, vesicle-based NPs, including niosomes, transferosomes, ethosomes, microemulsions, transfersomes, and exosomes, are also discussed. In addition, transdermal immunotherapy using vaccines has been reviewed for Ebola, Neisseria gonorrhoeae, Hepatitis B virus, Influenza virus, respiratory syncytial virus, Hand-foot-and-mouth disease, and Tetanus.

The Antibacterial Effect of Ciprofloxacin Loaded Calcium Carbonate (CaCO3) Nanoparticles Against the Common Bacterial Agents of Osteomyelitis.

The present study aimed to investigate the biocompatibility, antibacterial/anti-biofilm effects of ciprofloxacin-loaded calcium carbonate (Cip- loaded CaCO3) nanoparticles against the common organisms responsible for osteomyelitis. The antibacterial and biofilm inhibitory activities were studied by determination of minimum inhibitory concentrations (MICs) and minimum biofilm inhibitory concentrations (MBICs), respectively. Hemolytic effects were determined for studying hemocompatibility. The SDS-PAGE method was used to study the interaction of Cip- loaded CaCO3 with plasma proteins. The effects of Cip- loaded CaCO3 on the cell viability of human bone marrow mesenchymal stem cells (hBM-MSCs) was detected. The Cip- loaded CaCO3 nanoparticles were shown a significant antimicrobial effect at lower concentrations than free ciprofloxacin. No significant hemolytic effect was observed. The Cip- loaded CaCO3 nanoparticles have shown interaction with apolipoprotein A1 (28 kDa) and albumin (66.5 kDa). The viability of hBM-MSCs treated with Cip- loaded CaCO3 was more than 96%. Our results indicated that Cip-loaded CaCO3 nanoparticles had favorable in vitro compatibility with human red blood cells, antimicrobial effects, and low cytotoxicity.

Advances in Aptamers-Based Applications in Breast Cancer: Drug Delivery, Therapeutics, and Diagnostics.

Aptamers are synthetic single-stranded oligonucleotides (such as RNA and DNA) evolved in vitro using Systematic Evolution of Ligands through Exponential enrichment (SELEX) techniques. Aptamers are evolved to have high affinity and specificity to targets; hence, they have a great potential for use in therapeutics as delivery agents and/or in treatment strategies. Aptamers can be chemically synthesized and modified in a cost-effective manner and are easy to hybridize to a variety of nano-particles and other agents which has paved a way for targeted therapy and diagnostics applications such as in breast tumors. In this review, we systematically explain different aptamer adoption approaches to therapeutic or diagnostic uses when addressing breast tumors. We summarize the current therapeutic techniques to address breast tumors including aptamer-base approaches. We discuss the next aptamer-based therapeutic and diagnostic approaches targeting breast tumors. Finally, we provide a perspective on the future of aptamer-based sensors for breast therapeutics and diagnostics. In this section, the therapeutic applications of aptamers will be discussed for the targeting therapy of breast cancer.

Engineered nanoparticles as emerging gene/drug delivery systems targeting the nuclear factor-κB protein and related signaling pathways in cancer.

The transcription factor nuclear factor-κB (NF-κB) is a critical regulator of the immune response, inflammation, cell growth, and survival. Canonical and non-canonical pathways, two NF-κB pathways, are activated through diverse stimulators and receptors. NF-κB activity is dysregulated in various inflammation-related diseases and cancers. It was found that the persistent NF-κB activity has a major role in proliferation, apoptosis inhibition, metastasis, and cell cycle disruption in cancer cells and also the survival of cancer stem cells (CSCs) within the tumors. Therefore, suppression of the NF-κB pathway could be a promising therapeutic target for cancer therapy. Different biological inhibitors (e.g., peptides, small molecules, antisense oligonucleotides (ASOs), and antibodies (Abs)) have been demonstrated to inhibit the NF-κB pathway. Low stability in the circulation system, weak availability, and poor cellular uptake of some inhibitors limit their therapeutic applications. To address these drawbacks nanocarrier systems are often formulated and applied in drug delivery as an effective therapeutic approach. Targeted nanosystems (i.e., small molecules, peptides, Abs and Aptamers (Aps) conjugated nanocarriers), as well as smart responsive nanocarriers, can improve the efficiency of therapeutics while reducing the off-target toxicity. This review describes the NF-κB signaling pathways and mechanisms of their over-activation in tumor initiation and progression. The NF-κB inhibitors and their clinical applications are also discussed. It also overviews different nanocarriers used as robust vehicles for the delivery of NF-κB inhibitors and anti-tumor agents to improve the bioavailability of drugs and selective targeting of cancer cells to repress NF-κB activity in tumor cells.

Hollow pollen grains as scaffolding building blocks in bone tissue engineering.

Introduction: The current study, for the first time, suggests nature-made pollen grains (PGs) of Pistacia vera L. as a potential candidate for using as scaffolding building blocks with encapsulation capability of bioactive compounds, such as bone morphogenetic protein 4 (BMP4). Methods: A modified method using KOH (5%, 25ºC) was developed to produce nonallergic hollow pollen grains (HPGs), confirmed by energy dispersive X-ray (EDX) analysis, field emission scanning electron microscopy (FESEM), and DNA and protein staining techniques. The in-vitro study was conducted on human adipose-derived mesenchymal stem cells (hAD-MSCs) to investigate the applicability of HPGs as bone scaffolding building blocks. Cytocompability was evaluated by FESEM, MTT assay, and gene expression analysis of apoptotic markers (BAX and BCL2). The osteoconductive potential of HPGs was assessed by alkaline phosphatase (ALP) activity measurement and gene expression analysis of osteogenic markers (RUNX2 and osteocalcin). Results: Findings demonstrated that HPGs can be considered as biocompatible compounds increasing the metabolic activities of the cells. Further, the bioactive nature of HPGs resulted in suitable cellular adhesion properties, required for a potent scaffold. The investigation of apoptotic gene expression indicated a reduced BAX/BCL2 ratio reflecting the protective effect of HPGs on hAD-MSCs. The increased ALP activity and expression of osteogenic genes displayed the osteoconductive property of HPGs. Moreover, the incorporation of BMP4 in HPGs initiated a synergistic effect on osteoblast maturation. Conclusion: Owing to the unique compositional and surface nanotopographical features of the Pistacia vera L. HPG, this microscale architecture provides a favorable microenvironment for the bottom-up remodeling of bone.

Multifunctional magnetic nanoparticles for MRI-guided co-delivery of erlotinib and L-asparaginase to ovarian cancer.

The use of magnetic nanoparticles (MNPs) in biomedical applications has been wildly opted due to their unique properties. Here, we designed MNPs loaded with erlotinib (ERL/SPION-Val-PEG) and conjugated them with anti-mucin16 (MUC16) aptamer to introduce new image-guided nanoparticles (NPs) for targeted drug delivery as well as non-invasive magnetic resonance imaging (MRI) contrast agents. Also, the combination of our nanosystem (NS) along with L-Asparaginase (L-ASPN) led to synergistic effects in terms of reducing cell viability in ovarian cancer cells, which could suggest a novel combination therapy. The mean size of our NS was about 63.4 ± 3.4 nm evaluated by DLS analysis and its morphology was confirmed using TEM. Moreover, the functional groups, as well as magnetic properties of our NS, were examined by FT-IR and VSM tests, respectively. The loading efficacy of erlotinib on MNPs was about 80% and its release reached 70.85% over 7 days in the pH value of 5.4. The MR images and flow cytometry results revealed that the cellular uptake of ERL/SPION-Val-PEG-MUC16 NPs in cells with MUC16 overexpression was considerably higher than unarmed NPs. In addition, T2-weight MR images of ovarian cancer-bearing mice indicated significant signal intensity changes at the tumour site 4 h after intravenous injection compared to the non-target MNPs. Our data suggest ERL/SPION-Val-PEG NPs as an image-guided co-drug delivery system for ovarian cancer.

Electrospun nanofibers based on carboxymethyl cellulose/polyvinyl alcohol as a potential antimicrobial wound dressing.

In this work, citric acid-based quantum dots (CA-QDs) as a novel and safe crosslinked agent was applied in different feeding ratios (5-15 wt%) to synthesize carboxymethyl cellulose/polyvinyl alcohol (CMC/PVA) nanofibers (NFs) for the first time. Colistin (CL) as an antibacterial agent was also loaded (2 w/w%) during the synthesizing process of CMC/PVA electrospun NFs to trigger antimicrobial properties. The morphological, hydrophilic, and mechanical properties of the prepared NFs were fully investigated with different techniques. The electrospun NFs with crosslinking ratios of 10 wt% CA-QDs revealed appropriate mechanical properties. According to cell culture data, the prepared NFs demonstrated good cytocompatibility against HFF-1 cells (over 80% cell viability). Remarkably, CL-loaded NFs showed desired antibacterial efficacy against S. aureus, E. coli, K. pneumoniae, and P. aeruginosa with 1.0-1.4, 1.3-1.4, 0.8-1.0, and 1.3-1.5 cm inhibition zones, respectively. These outcomes suggested that the fabricated NFs can be useful as wound healing scaffolds.

Bioactive Chitosan-Based Organometallic Scaffolds for Tissue Engineering and Regeneration.

Captivating achievements in developing advanced hybrid biostructures through integrating natural biopolymers with inorganic materials (e.g., metals and metalloids) have paved the way towards the application of bioactive organometallic scaffolds (OMSs) in tissue engineering and regenerative medicine (TERM). Of various biopolymers, chitosan (CS) has been used widely for the development of bioactive OMSs, in large part due to its unique characteristics (e.g., biocompatibility, biodegradability, surface chemistry, and functionalization potential). In integration with inorganic elements, CS has been used to engineer advanced biomimetic matrices to accommodate both embedded cells and drug molecules and serve as scaffolds in TERM. The use of the CS-based OMSs is envisioned to provide a new pragmatic potential in TERM and even in precision medicine. In this review, we aim to elaborate on recent achievements in a variety of CS/metal, CS/metalloid hybrid scaffolds, and discuss their applications in TERM. We also provide comprehensive insights into the formulation, surface modification, characterization, biocompatibility, and cytotoxicity of different types of CS-based OMSs.

Synthesis and biological impacts of pollen shells/Fe3O4 nanoparticles composites on human MG-63 osteosarcoma cells.

INTRODUCTION: Cell-adhesive surfaces play a pivotal role in biomedical engineering, as most biological reactions take place on surfaces. Pollen shell (PSh) ofPistacia vera L., as a new medical device, has previously been reported to cause cytotoxicity and apoptosis in MG-63 bone cancer cells. METHODS: Iron oxide nanoparticles (Fe3O4NPs) were synthesized and their reaction to PShs was gauged at different concentrations, and then characterized using field emission scanning electron microscopy (FESEM), Fourier-transform infrared spectroscopy, energy dispersion X-ray spectrometer, X-ray diffraction spectra, dynamic light scattering, and vibrating sample magnetometer. Then, the biological impacts of PShs/Fe3O4NPs composites on MG-63 cells were investigated in-vitro using MTT assay, quantitative polymerase chain reaction (qPCR), Annexin V/propidium iodide, FESEM, and DAPI staining. RESULTS: Fe3O4NPs with a size range of 24-40 nm and a zeta potential value of -37.4 mV were successfully assembled on the PShs. The viability of MG-63 cells was significantly decreased when cultured on the magnetic PShs as compared to non-magnetic PShs, in Fe3O4 concentration and time-dependent manner. In contrast, magnetic PShs had a positive effect on the viability of normal human bone marrow-derived mesenchymal stem cells (hBM-MSCs). The analysis of apoptosis-related genes in cancer cells revealed that loading Fe3O4NPs on PShs increased expression of BAX/BCL2 and caspase-3 genes. The increased apoptotic activity of combined PShs/Fe3O4NPs was further confirmed by flow cytometric measurement, morphological analysis, and DAPI staining. CONCLUSION: The incorporation of Fe3O4NPs into PShs could effectively increase anticancer effects on MG-63 cells via the mitochondria-mediated apoptosis pathway, evident by upregulation of BAX/BCL2 ratio and caspase-3.

Nanomaterials and Stem Cell Differentiation Potential: An Overview of Biological Aspects and Biomedical Efficacy.

Nanoparticles (NPs), due to their medical applications, are widely used. Accordingly, the use of mesenchymal stem cells is one of the most important alternatives in the tissue engineering field. NPs play effective roles in stem cells proliferation and differentiation. The combination of NPs and tissue regeneration by stem cells has created a new therapeutic approach towards humanity. Of note, the physicochemical properties of NPs determine their biological function. Interestingly, various mechanisms such as modulation of signaling pathways and generation of reactive oxygen species, are involved in NPs-induced cellular proliferation and differentiation. This review summarized the types of nanomaterials effective on stem cell differentiation, the physicochemical features, biomedical application of these materials and the relationship between nanomaterials and environment.

In-vitro Effect of Imipenem, Fosfomycin, Colistin, and Gentamicin Combination against Carbapenem-resistant and Biofilm-forming Pseudomonas aeruginosa Isolated from Burn Patients.

The aim of this study was to investigate in-vitro antibacterial and antibiofilm effect of colistin, imipenem, gentamicin, and fosfomycin alone and the various combinations against carbapenem-resistant Pseudomonas aeruginosa (P. aeruginosa). Eight carbapenem-resistant and biofilm-forming P. aeruginosa isolates from burn patients were collected. The mechanisms of resistance to carbapenem were determined by the phenotypic, PCR, and Real-Time PCR assays. The minimum inhibitory concentration (MIC) of antimicrobial agents was determined by the broth micro dilution. To detect any inhibitory effect of antibiotics against the biofilm, the biofilm inhibitory concentration was determined. To detect synergetic effects of the combinations of antibiotics, the checkerboard assay and the fractional inhibitory concentration (FIC) were used. The highest synergic effect was observed in colistin/fosfomycin and gentamicin/fosfomycin (5 of 8 isolates), and the lowest synergic effect was found in gentamicin/imipenem and colistin/gentamicin (1 of 8 isolates). Colistin/fosfomycin, imipenem/fosfomycin, colistin/imipenem, gentamicin/fosfomycin, and gentamicin/imipenem were shown synergic effect for 3, 2, 2, 2 and 1 isolates, respectively. The combination of antibiotics had different effects on biofilm and planktonic forms of P. aeruginosa. Therefore, a separate determination of inhibitory effects of the antibiotic in the combination is necessary. Fosfomycin/colistin and fosfomycin/gentamicin were more effective against planktonic form and fosfomycin/colistin against biofilm forms.

Stimuli-responsive graphene oxide and methotrexate-loaded magnetic nanoparticles for breast cancer-targeted therapy.

Aim: Nanocomposites of graphene oxide (GO) loaded with PEGylated superparamagnetic iron oxide nanoparticles and grafted with methotrexate and stimuli-responsive linkers (GO-SPION-MTX) were developed for photothermal and chemotherapy of breast cancer. Methods: PEGylated SPIONs were synthesized and conjugated with chemotherapeutic targeting agent MTX, which were then loaded on GO to prepare GO-SPION-MTX nanocomposites. To evaluate the photothermal effect of the nanocomposites, they were examined in breast cancer cell lines with low doses of near-infrared (NIR) laser radiation with/without acetazolamide. Results: The GO-SPION-MTX nanocomposites were found to be internalized by the folate-receptor-positive cancer cells and induce high cytotoxicity on exposure to NIR laser rays. Conclusion: Our findings suggest that the GO-SPION-MTX nanocomposite can potentially be used as a multimodal nanomedicine/theranostic against breast cancer.

Folate receptor-mediated delivery of 1-MDT-loaded mesoporous silica magnetic nanoparticles to target breast cancer cells.

Aims: The efficiency of mesoporous silica magnetic nanoparticles (MSMNP) as a targeted drug-delivery system was investigated. Methods: The superparamagnetic iron oxide nanoparticles (NP) were synthesized, coated with mesoporous silica and conjugated with polyethylene glycol and methotrexate. Next, 1-methyl-D-tryptophan was loaded into the prepared nanosystems (NS). They were characterized using transmission electron microscopy, scanning electron microscopy, dynamic light scattering, vibrating sample magnetometer, x-ray powder diffraction, Fourier transform-infrared spectroscopy and the Brunauer-Emmett-Teller method and their biological impacts on breast cancer cells were evaluated. Results: The prepared NSs displayed suitable properties and showed enhanced internalization by folate-receptor-expressing cells, exerting efficient cytotoxicity, which was further enhanced by the near-infrared radiation irradiation. Conclusion: On the basis of our findings, the engineered NS is a promising multifunctional nanomedicine/theranostic for solid tumors.

Targeted combined therapy in 2D and 3D cultured MCF-7 cells using metformin and erlotinib-loaded mesoporous silica magnetic nanoparticles.

AIM: This research aims to develop potential therapeutic nanostructures (NSs) encapsulating metformin (MET) and erlotinib (ER) for combinational therapy in breast cancer. METHODS: The ER and MET, both were loaded on mesoporous silica magnetic nanoparticles conjugated with polyethylene glycol and methotrexate to achieve targeted NSs. The developed NSs were characterised using SEM, DLS, and FTIR. Afterward, MTT, Trypan blue, and DNA extraction assays were operated for biological evaluations in the 2D and 3D MCF-7 cells. RESULTS: Physicochemical approaches indicated the mean diameter of 69.4 nm ± 9.5 (PDI = 0.64), and neutral charge (2 mv) for the developed NSs. MET and ER-loaded NSs exhibited 62.56% ± 4.41 and 67.73% ± 3.03 drug release amount in pH = 5.4, respectively. MTT assay revealed that ER- and MET-loaded NSs had less metabolic activity (≈ 20%) in comparison with non-targeted NSs. CONCLUSION: Overall, our combined ER and MET-loaded targeted NSs result in a synergistic inhibitory impact on MCF-7 cells.

Silver nanoparticles induce the cardiomyogenic differentiation of bone marrow derived mesenchymal stem cells via telomere length extension.

Finding new strategies for the treatment of heart failures using stem cells has attracted a lot of attention. Meanwhile, nanotechnology-based approaches to regenerative medicine hypothesize a possible combination of stem cells and nanotechnology in the treatment of diseases. This study aims to investigate the in vitro effect of silver nanoparticles (Ag-NPs) on the cardiomyogenic differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs) through detection of cardiac markers. For this purpose, MSCs were isolated from bone marrow resident and differentiated to the cardiac cells using a dedicated medium with Ag-NPs. Also, the cardiomyogenic differentiation of BM-MSCs was confirmed using immunocytochemistry. Then, real-time PCR and western blotting assay were used for measuring absolute telomere length (TL) measurement, and gene and protein assessment of the cells, respectively. It was found that 2.5 µg/mL Ag-NPs caused elongation of the telomeres and altered VEGF, C-TnI, VWF, SMA, GATA-4, TERT, and cyclin D protein and gene expression in the cardiomyogenically differentiated BM-MSCs. Also, there was a significant increase in the protein and gene expression of Wnt3 and ß-catenin as main components of pathways. We concluded that Ag-NPs could change the in vitro expression of cardiac markers of BM-MSCs via the Wnt3/ß-catenin signaling pathway.

Preparation, Physicochemical Characterization and Anti-Fungal Evaluation of Amphotericin B-Loaded PLGA-PEG-Galactosamine Nanoparticles.

Purpose: The present study aimed to formulate PLGA and PLGA-PEG-galactosamine nanoparticles (NPs) loaded with amphotericin B with appropriate physicochemical properties and antifungal activity. PLGA was functionalized with GalN to increase the adhesion and antifungal activity of NPs against Candida albicans. Methods: The physicochemical properties of NPs were characterized by particle size determination, zeta potential, drug crystallinity, loading efficiency, dissolution studies, differential scanning calorimeter (DSC), X-ray powder diffraction (XRPD), and Fourier transform infrared (FT-IR). Antifungal activity of the NPs at different drug/polymer ratios was examined by determining minimum inhibitory concentrations (MICs). Results: the FT-IR and 1 HNMR analysis successfully confirmed the formation of PLGA- PEG-GalN NPs. The PLGA NPs were in the size range of 174.1 ± 3.49 to 238.2±7.59 nm while PLGA-GalN NPs were 255.6 ±4.08 nm in size , respectively. Loading efficiency was in the range of 67%±2.4 to 77%±1.6, and entrapment efficiency in the range of 68.185%±1.9 to 73.05%±0.6. Zeta potential and loading efficiency for PLGA-GalN NPs were -0.456, 71%. The NPs indicated an amorphous status according to XRPD patterns and DSC thermograms. The PLGA-PEG-GalN NPs showed higher fungistatic activity than PLGA NPs. Conclusion: the results demonstrated that the antifungal activity of PLGA-PEG-GalN NPs was higher than pure amphotericin B and PLGA NPs.