Alpha terpineol preconditioning enhances regenerative potential of mesenchymal stem cells in full thickness acid burn wounds.

Regeneration of full thickness burn wounds is a significant clinical challenge. Direct stem cell transplantation at the wound site has a promising effect on wound regeneration. However, stem cell survival within the harsh wound environment is critically compromised. In this regard, preconditioning of stem cells with cytoprotective compounds can improve the efficiency of transplanted cells. This study evaluated the possible effect of alpha terpineol (αT) preconditioned mesenchymal stem cells (αT-MSCs) in full thickness acid burn wound. An optimized concentration of 10 µM αT was used for MSC preconditioning, followed by scratch assay analysis. A novel rat model of full thickness acid burn wound was developed and characterized via macroscopic and histological examinations. Treatment (normal and αT-MSCs) was given after 48 h of burn wound induction, and the healing pattern was examined till day 40. Skin tissues were harvested at the early (day 10) and late (day 40) wound healing phases and examined by histological grading, neovascularization, and gene expression profiling of healing mediators. In scratch assay, αT-MSCs exhibited enhanced cell migration and wound closure (scratch gap) compared to normal MSCs. In vivo findings revealed enhanced regeneration in the wound treated with αT-MSCs compared to normal MSCs and untreated control. Histology revealed enhanced collagen deposition with regenerated skin layers in normal MSC- and αT-MSC treated groups compared to the untreated control. These findings were correlated with enhanced expression of α-SMA as shown by immunohistochemistry. Additionally, αT-MSC group showed reduced inflammation and oxidative stress, and enhanced regeneration, as witnessed by a decrease in IL-1ß, IL-6, TNF-α, and Bax and an increase in BCL-2, PRDX-4, GPX-7, SOD-1, VEGF, EGF, FGF, MMP-9, PDGF, and TGF-ß gene expression levels at early and late phases, respectively. Overall findings demonstrated that αT exerts its therapeutic effect by mitigating excessive inflammation and oxidative stress while concurrently enhancing neovascularization. Thus, this study offers new perspectives on managing full thickness acid burn wounds in future clinical settings.

Single dose human perinatal stem cells accelerate healing of cold-induced rat burn wound.

Temporal phases of wound healing and their corresponding healing factors are essential in wound regeneration. Mesenchymal stem cells (MSCs) accelerate wound healing via their paracrine secretions by enhancing cell migration, angiogenesis, and reducing inflammation. This study evaluated the local therapeutic effect of human umbilical cord MSCs (hUCMSCs) in the healing of cold-induced burn wounds. An in vitro wound (scratch) was developed in rat skin fibroblasts. The culture was maintained in the conditioned medium (CM) which was prepared by inducing an artificial wound in hUCMSCs in a separate experiment. Treated fibroblasts were analyzed for the gene expression profile of healing mediators involved in wound closure. Findings revealed enhanced cell migration and increased levels of healing mediators in the treated fibroblasts relative to the untreated group. Cold-induced burn wounds were developed in Wistar rats, followed by a single injection of hUCMSCs. Wound healing pattern was examined based on the healing phases: hemostasis/inflammation (Days 1, 3), cell proliferation (Day 7), and remodeling (Day 14). Findings exhibited enhanced wound closure in the treated wound. Gene expression, histological, and immunohistochemical analyses further confirmed enhanced wound regeneration after hUCMSC transplantation. Temporal gene expression profile revealed that the level of corresponding cytokines was substantially increased in the treated wound as compared with the control, indicating improvement in the processes of angiogenesis and remodeling, and a substantial reduction in inflammation. Histology revealed significant collagen formation along with regenerated skin layers and appendages, whereas immunohistochemistry exhibited increased neovascularization during remodeling. Leukocyte infiltration was also suppressed in the treated group. Overall findings demonstrate that a single dose of hUCMSCs enhances wound healing in vivo, and their secreted growth factors accelerate cell migration in vitro.

Preparation of novel shell-ionotropically crosslinked micelles based on hexadecylamine and tripolyphosphate for cancer drug delivery.

AIMS: Micellar systems have the advantage of being easily prepared, cheap, and readily loadable with bioactive molecular cargo. However, their fundamental pitfall is poor stability, particularly under dilution conditions. We propose to use simple quaternary ammonium surfactants, namely, hexadecylamine (HDA) and hexadecylpyridinium (HDAP), together with tripolyphosphate (TPP) anion, to generate ionotropically stabilized micelles capable of drug delivery into cancer cells. METHODS: optimized mixed HDA/HDAP micelles were prepared and stabilized with TPP. Curcumin was used as a loaded model drug. The prepared nanoparticles were characterized by dynamic light scattering, infrared spectroscopy, transmission electron microscopy, and differential scanning calorimetry. Moreover, their cellular uptake was assessed using flow cytometry and confocal fluorescence microscopy. RESULTS: The prepared nanoparticles were found to be stable under dilution and at high temperatures and to have a size range from 139 nm to 580 nm, depending on pH (4.6-7.4), dilution (up to 100 times), and temperature (25 - 80 °C). They were effective at delivering their load into cancer cells. Additionally, flow cytometry indicated the resulting stabilized micellar nanoparticles to be non-cytotoxic. CONCLUSIONS: The described novel stabilized micelles are simple to prepare and viable for cancer delivery.

Studying Microbial Ecology of Diabetic Foot Infections: Significance of PCR Analysis for Prudent Antimicrobial Stewardship.

This study presents a comprehensive investigation into the microbial ecology of diabetic foot infections (DFIs), using molecular-polymerase chain reaction (PCR) analysis to accurately identify the causative agents. One hundred DFI patients were recruited and classified using the Depth Extent Phase and Associated Etiology (DEPA) score according to their severity. Results revealed polymicrobial infections in 75% of cases, predominantly featuring Staphylococcus epidermidis (83%) and Staphylococcus aureus (63%). Importantly, 20% of samples exhibited facultative anaerobes Bacteroides fragilis or Clostridium perfringens, exclusively in high DEPA score ulcers. Candida albicans coinfection was identified in 19.2% of cases, underscoring the need for mycological evaluation. Empirical antimicrobial therapy regimens were tailored to DEPA severity, yet our findings highlighted a potential gap in methicillin-resistant Staphylococcus aureus (MRSA) coverage. Despite an 88% prevalence of methicillin-resistant Staphylococci, vancomycin usage was suboptimal. This raises concerns about the underestimation of MRSA risk and the need for tailored antibiotic guidelines. Our study demonstrates the efficacy of molecular-PCR analysis in identifying diverse microbial communities in DFIs, influencing targeted antibiotic choices. The results advocate for refined antimicrobial guidelines, considering regional variations in microbial patterns and judiciously addressing multidrug-resistant strains. This research contributes crucial insights for optimizing DFIs management and helps the physicians to have a fast decision in selection the suitable antibiotic for each patient and to decrease the risk of bacterial resistance from the improper use of broad-spectrum empirical therapies.

Bactericidal effect of Iberin combined with photodynamic antimicrobial chemotherapy against Pseudomonas aeruginosa biofilm cultured on ex vivo wound model.

Wounds infected by Pseudomonas aeruginosa (P. aeruginosa) biofilms are characterized by poor healing and by being long lasting. Pyocyanin and pyoverdine are exotoxins that contribute to P. aeruginosa pathogenicity in wound infections and are known as virulence factors. Despite the usefulness of antimicrobial photodynamic therapy (PDT) in the management of wound infections, biofilms are hurdle for microbial photoinactivation. Quorum sensing (QS) is a cell density-dependent chemical signaling system P. aeruginosa uses to regulate biofilm formation and virulence factors production. In the current study, QS attenuation was used in combination with PDT against P. aeruginosa biofilm cultured on skin explant. Iberin is a QS inhibitor that attenuates P. aeruginosa virulence and affects biofilm integrity. The antibiofilm and QS inhibitory activities of iberin in combination with either riboflavin or 5,10,15,20-Tetrakis(1-methyl-4-pyridinio) porphyrin tetra p-toluenesulfonate (TMP) mediated PDT were investigated using viable count method and pyocyanin and pyoverdine assays, respectively. No bactericidal activity was reported when iberin was added to a mature biofilm (24 h) followed by PDT. When added to a growing biofilm at multiple time points (0 h, 24 h and 48 h), iberin inhibited P. aeruginosa biofilm QS signaling system. This inhibitory effect resulted in an observable decrease in the levels of the QS-regulated virulence factors, pyocyanin and pyoverdine, without any effect on the growth of the biofilm cultures. These changes in biofilm virulence were associated with a decrease in biofilm resistance to PDT and caused bactericidal effect upon photosensitizers treatment and irradiation. Iberin-treated-riboflavin-mediated PDT resulted in a significant 1.3 log reduction in biofilm population. Similarly, iberin-treated-TMP-mediated PDT caused a significant 1.8 log reduction in biofilm population. The combination of QS inhibitor with PDT is a promising alternative antimicrobial therapy for the management of biofilms.

Rapid integration of screen-printed electrodes into thermoplastic organ-on-a-chip devices for real-time monitoring of trans-endothelial electrical resistance.

Trans-endothelial electrical resistance (TEER) is one of the most widely used indicators to quantify the barrier integrity of endothelial layers. Over the last decade, the integration of TEER sensors into organ-on-a-chip (OOC) platforms has gained increasing interest for its efficient and effective measurement of TEER in OOCs. To date, microfabricated electrodes or direct insertion of wires has been used to integrate TEER sensors into OOCs, with each method having advantages and disadvantages. In this study, we developed a TEER-SPE chip consisting of carbon-based screen-printed electrodes (SPEs) embedded in a poly(methyl methacrylate) (PMMA)-based multi-layered microfluidic device with a porous poly(ethylene terephthalate) membrane in-between. As proof of concept, we demonstrated the successful cultures of hCMEC/D3 cells and the formation of confluent monolayers in the TEER-SPE chip and obtained TEER measurements for 4 days. Additionally, the TEER-SPE chip could detect changes in the barrier integrity due to shear stress or an inflammatory cytokine (i.e., tumor necrosis factor-α). The novel approach enables a low-cost and facile fabrication of carbon-based SPEs on PMMA substrates and the subsequent assembly of PMMA layers for rapid prototyping. Being cost-effective and cleanroom-free, our method lowers the existing logistical and technical barriers presenting itself as another step forward to the broader adoption of OOCs with TEER measurement capability.

IR microspectroscopic investigation of the interaction of some losartan salts with human stratum corneum protein and its effect on losartan transdermal permeation.

The interaction of pharmacologically active drugs with SC biochemical components is underestimated in pharmaceutical research. The aim of this research was to illustrate that some drugs intended for transdermal delivery could interact with the protein component of SC. Such interactions could be in favor of or opposition to their percutaneous absorption. IR microspectroscopy was used to delineate possible interaction of SC keratin with three losartan salts LOS-K, LOS-DEA and LOS-AML salts in addition to AML-BES salt. The results of PCA, combined with comparisons of average second derivative spectra of SC samples treated with these salts and the control SC, showed that LOS-DEA did not interact with SC, thus providing base line permeation of losartan. AML-BES, LOS-AML and LOS-K salts modified the conformational structure of keratin. The disorganization effect on the α-helical structure and induced formation of parallel ß-sheets and random coils were in the order of AML-BES˃LOS-AML˃LOS-K. The order of the impact of treatments which resulted in increased formation of ß-turns was AML-BES˃LOS-AML. The formation of antiparallel ß-sheets was manifested by LOS-AML. Thus, the overall effect of these salts on the SC protein was AML-BES˃LOS-AML˃LOS-K. The impact of LOS-K was associated with improved permeation whereas the impact of LOS-AML was associated with hindered permeation of both losartan and amlodipine. There is a possibility that losartan and amlodipine when present in combination inside SC, their binding to the protein is enhanced leading to being retained within SC.

Synchrotron-Radiation-Based Fourier Transform Infrared Microspectroscopy as a Tool for the Differentiation between Staphylococcal Small Colony Variants.

Small colony variants (SCVs) are clinically significant and linked to persistent infections. In this study, synchrotron-radiation-based Fourier transform infrared (SR-FTIR) is used to investigate the microspectroscopic differences between the SCVs of Staphylococcus aureus (S. aureus) and diabetic foot Staphylococcus epidermidis (S. epidermidis) in two main IR spectral regions: (3050-2800 cm-1), corresponding to the distribution of lipids, and (1855-1500 cm-1), corresponding to the distribution of protein amide I and amide II and carbonyl vibrations. SR-FTIR successfully discriminated between the two staphylococcal species and between the SCV and the non-SCV strains within the two IR spectral regions. Combined S. aureus SCVs (SCVhMu) showed a higher protein content relative to the non-SCV wild type. Complemented S. aureus SCV showed distinguishable differences from the SCVhMu and the wild type, including a higher content of unsaturated fatty acids. An increase in the CH2/CH3 ratio was detected in S. epidermidis SCV samples compared to the standard control. Protein secondary structure in standard S. epidermidis and SCVs consisted mainly of an α-helix; however, a new shoulder at 1635 cm-1, assigned to ß-sheets, was evident in the SCV. In conclusion, SR-FTIR is a powerful method that can discriminate between staphylococci species and to differentiate between SCVs and their corresponding natural strains.

Formulation and Evaluation of Eudragit® RL Polymeric Double Layer Films for Prolonged-Release Transdermal Delivery of Tamsulosin Hydrochloride.

Transdermal drug delivery systems (TDDSs) were developed for prolonged tamsulosin (TMS) delivery. Double layer (DL) TDDSs were prepared using Eudragit® RL by conventional film-forming. Ethylene-vinyl acetate was used as the backing layer, triethylcitrate as plasticizer, and Capmul® PG-8-70 NF and Captex 170 EP as penetration enhancers (PEs). An increase in either drug or PE concentration caused a significant increase in drug permeation flux. Modulation of drug permeation across Strat-M® membrane was examined using a single layer (SL) having the same thickness and drug content as the DLs, while the DLs were formulated to have variable drug spatial distribution across each layer (DL 4:6 and DL 6:4). SL/TDDS showed significantly higher daily drug permeation than DL/TDDSs for the first 4 days which could be related to the presence of high TMS concentration located on the upper surface of SL/TDDS as a result of solute migration of TMS during the drying process. However, this increase was followed by a progressive linear decrease after 5 days. Deflection points that were characterized by lower drug flux had been shown by SL/TDDS at more than one-point times. In contrast, DL 4:6 and DL 6:4 TDDSs demonstrated an ability to sustain TMS delivery for up to 2 weeks.

Interaction of esomeprazole with insulin detemir and human albumin: A potential cause of hypoglycemia.

Insulin detemir (IDt) is long-acting insulin whose protraction mechanism is based on a covalently attached fatty acid to an insulin molecule. Utilizing the high affinity of fatty acids towards human serum albumin (HA), the modified detemir molecule binds with good affinity to HA, which functions as a reservoir that leads to a slow and prolonged release of insulin. However, questions were raised over potential interactions between other drugs and IDt through competitive binding on the binding site(s) of HA. In a previous study, concomitant use of esomeprazole (Esom) and erythromycin resulted in severe hypoglycemia, and thus: the drugs including Esom were suggested as enhancers of IDt action through displacing it from its binding site on HA. To further study this possibility, studies utilizing different techniques including, semipermeable membrane dialysis, capillary electrophoresis, UV,NMR spectroscopy, and molecular docking were carried out. Results from various techniques supported the simultaneous binding of Esom along with IDt to HA (i.e., binding in two different sites without signs of competition between the two). Moreover, capillary electrophoresis suggested an increase in the binding affinity of Esom to HA in the presence of IDt (1.9 × 103 Vs 2.7 × 104M-1). Perhaps most interesting was the observation that Esom could bind directly to IDt which was evidenced by all the employed techniques. Direct binding of Esom to IDt, might explain the enhancement in insulin action associated with the concomitant use of Esom. Therefore, Esom might represent a leading insulin-sensitizing compound that might lead to more effective insulin enhancing and less unwanted effects.

The In Vitro Immunomodulatory Effects of Gold Nanocomplex on THP-1-Derived Macrophages.

Introduction: This study is aimed at investigating the immunological response after treating THP-1 cells with gold nanorods conjugated with a phosphatidylinositol 3-kinase (PI3Kα) inhibitor. Methodology. Gold nanorods were synthesized and functionalized with cholesterol-PEG-SH moiety, and the treatment groups were as follows: nanocomplex (a drug-conjugated gold nanorods), free drug (phosphatidylinositol 3-kinase (PI3Kα) inhibitor), and GNR (the nanocarrier; cholesterol-coated gold nanorods). THP-1 cells were differentiated into macrophages and characterized by measuring the expression of macrophage surface markers by flow cytometry. Then, differentiated cells were activated by lipopolysaccharide (LPS). Afterwards, activated macrophages were treated with the different treatments: nanocomplex, free drug, and GNR, for 24 hrs. After treatment, the production of the inflammatory cytokines measured at gene and protein levels by using qPCR and CBA array beads by flow cytometry. Results: Our results show that THP-1 cells were successfully differentiated into macrophages. For inflammatory cytokine expression response, nanocomplex and free drug showed the same expression level of cytokines at gene level, as the expression of IL-1ß, IL-6, and TNF-α was significantly downregulated (p < 0.0005, p < 0.0005, p < 0.00005), respectively, while IL-8, IL-10, and TGF-ß were all upregulated in a significant manner for nanocomplex (p < 0.00005, p < 0.00005, p < 0.00005) and free drug treatment group (p < 0.00005, p < 0.05, p < 0.05) compared to the control untreated group. While in the GNR group, IL-6 and TNF-α were downregulated (p < 0.005, p < 0.00005), and IL-12p40 (p < 0.00005) was upregulated all in a statistically significant manner. While at protein level, cells were treated with our nanocomplex: IL-1ß, IL-6, TNF-α, and IL-12p70 and were significantly decreased (p < 0.00005,p < 0.005,p < 0.05,p < 0.00005), and IL-10 was found to be significantly increased in culture compared to the untreated control group (p < 0.005). For free drug; IL-1ß and IL-12p70 were significantly decreased (p < 0.00005, p < 0.00005), while a significant increase in the secretion levels of IL-10 only was noticed compared to the untreated group (p < 0.005). For GNR treatment groups, IL-1ß, TNF-α, and IL-12p70 were significantly decreased (p < 0.00005, p < 0.05, p < 0.00005). Conclusion: We can conclude that our nanocomplex is a potent effector that prevents tumoral progression by activating three main immunological strategies: switching the surface expression profile of the activated macrophages into a proinflammatory M1-like phenotype, downregulating the expression of proinflammatory cytokines, and upregulating the expression level of anti-inflammatory cytokines.

Effect of Diluted Dakin's Solution Versus Standard Care on Diabetic Foot Ulcer Management: A Randomized Controlled Trial.

BACKGROUND: Diabetic foot ulcers (DFUs) are the main cause of hospitalizations and amputations in diabetic patients. Failure of standard foot care is the most important cause of impaired DFU healing. Dakin's solution (DS) is a promising broad-spectrum bactericidal antiseptic for management of DFUs. Studies investigating the efficacy of using DS on the healing process of DFUs are scarce. Accordingly, this is the first evidence-based, randomized, controlled trial conducted to evaluate the effect of using diluted DS compared with the standard care in the management of infected DFUs. METHODS: A randomized controlled trial was conducted to assess the efficacy of DS in the management of infected DFUs. Patients were distributed randomly to the control group (DFUs irrigated with normal saline) or the intervention group (DFUs irrigated with 0.1% DS). Patients were followed for at least 24 weeks for healing, reinfection, or amputations. In vitro antimicrobial testing on DS was performed, including determination of its minimum inhibitory concentration, minimum bactericidal concentration, minimum biofilm inhibitory concentration, minimum biofilm eradication concentration, and suspension test. RESULTS: Replacing normal saline irrigation in DFU standard care with 0.1% DS followed by soaking the ulcer with commercial sodium hypochlorite (0.08%) after patient discharge significantly improved ulcer healing (P < .001) and decreased the number of amputations and hospitalizations (P < .001). The endpoint of death from any cause (risk ratio, 0.13; P = .029) and the amputation rate (risk ratio, 0.27; P < .001) were also significantly reduced. The effect on ulcer closure (OR, 11.9; P < .001) was significantly enhanced in comparison with the control group. Moreover, DS irrigation for inpatients significantly decreased bacterial load (P < .001). The highest values for the in-vitro analysis of DS were as follows: minimum inhibitory concentration (MIC), 1.44%; minimum bactericidal concentration (MBC), 1.44%; minimum biofilm inhibitory concentration (MBIC), 2.16%; and minimum biofilm eradication concentration (MBEC), 2.87%. CONCLUSIONS: Compared with standard care, diluted DS (0.1%) was more effective in the management of infected DFUs. Dakin's solution (0.1%) irrigation with debridement followed by standard care is a promising method in the management of infected DFUs.

Correction: Mahmoud et al. Interaction of Gold Nanorods with Human Dermal Fibroblasts: Cytotoxicity, Cellular Uptake, and Wound Healing. Nanomaterials 2019, 9, 1131.

The authors wish to make the following correction to Figure 1 D in this paper [...].

Cytotoxicity and Cellular Death Modality of Surface-Decorated Gold Nanorods against a Panel of Breast Cancer Cell Lines.

Herein, the antiproliferative effect of surface-decorated gold nanorods (GNRs) was investigated against three different breast cancer cell lines. The results indicate that the cell lines exhibited different biological responses and death modalities toward the treatment. The cell lines exhibited similar cellular uptake of the nanoparticles; however, MDA-MB-231 demonstrated the highest cytotoxicity compared to other cell lines upon treatment with GNRs. The expression of the CDH1 gene, which is involved in cell adhesion and metastasis, was dramatically increased in treated MDA-MB-231 cells compared to other cell lines. Early apoptosis and late apoptosis are the dominant cellular death modalities of MDA-MB-231 cells upon treatment with GNRs.

Phospholipid-Gold Nanorods Induce Energy Crisis in MCF-7 Cells: Cytotoxicity Evaluation Using LC-MS-Based Metabolomics Approach.

Phospholipid-modified gold nanorods (phospholipid-GNRs) have demonstrated drastic cytotoxicity towards MCF-7 breast cancer cells compared to polyethylene glycol-coated GNRs (PEG-GNRs). In this study, the mechanism of cytotoxicity of phospholipid-GNRs towards MCF-7 cells was investigated using mass spectrometry-based global metabolic profiling and compared to PEGylated counterparts. The results showed that when compared to PEG-GNRs, phospholipid-GNRs induced significant and more pronounced impact on the metabolic profile of MCF-7 cells. Phospholipid-GNRs significantly decreased the levels of metabolic intermediates and end-products associated with cellular energy metabolisms resulting in dysfunction in TCA cycle, a reduction in glycolytic activity, and imbalance of the redox state. Additionally, phospholipid-GNRs disrupted several metabolism pathways essential for the normal growth and proliferation of cancer cells including impairment in purine, pyrimidine, and glutathione metabolisms accompanied by lower amino acid pools. On the other hand, the effects of PEG-GNRs were limited to alteration of glycolysis and pyrimidine metabolism. The current work shed light on the importance of metabolomics as a valuable analytical approach to explore the molecular effects of GNRs with different surface chemistry on cancer cell and highlights metabolic targets that might serve as promising treatment strategy in cancer.

HPLC method development/validation and skin diffusion study of caffeine, methyl paraben and butyl paraben as skin-diffusing model drugs.

The focus of this research was to develop and validate a suitable HPLC method, which allows simultaneous determination of three proposed skin model penetrants to investigate the percutaneous diffusion behavior of their combination: caffeine, methyl paraben and butyl paraben. These penetrants were selected because they represent a wide range of lipophilicities. This model highlights the effect of combining penetrants of different molecular properties on their diffusion behavior through skin. The proposed method employed a gradient system that was systematically optimized for separation and quantification of the penetrants. The effect of the stationary phase (C18, C4 and cyano (CN)) was assessed with CN proven to be superior in terms of peak shape, retentivity and dynamic linear range. Significant differences in retention time, peak broadening, and quantifiability between different stationary phases could be demonstrated. The method was validated as per ICH guidelines Q2 (R1) with a satisfactory outcome. The method was successfully applied for real diffusion experiments, and revealed notable differences between the individual penetrants and their ternary mixture on transdermal permeation. The method could potentially be extended to determine these analytes in other related skin permeation investigations.

Quercetin-gold nanorods incorporated into nanofibers: development, optimization and cytotoxicity.

Herein, a polymeric nanofiber scaffold loaded with Quercetin (Quer)-gold nanorods (GNR) was developed and characterized. Several parameters related to loading Quer into GNR, incorporating the GNR-Quer into polymeric solutions, and fabricating the nanofibers by electrospinning were optimized. GNR-Quer loaded into a polymeric mixture of poly(lactic-co-glycolic acid) (PLGA) (21%) and poloxamer 407 (23%) has produced intact GNR-Quer-nanofibers with enhanced physical and mechanical properties. GNR-Quer-nanofibers demonstrated a slow pattern of Quer release over time compared to nanofibers free of GNR-Quer. Dynamic mechanical thermal analysis (DMTA) revealed enhanced uniformity and homogeneity of the GNR-Quer-nanofibers. GNR-Quer-nanofibers demonstrated a high ability to retain water upon incubation in phosphate buffer saline (PBS) for 24 h compared to nanofibers free of GNR-Quer. A cellular toxicity study indicated that the average cellular viability of human dermal fibroblasts was 76% after 24 h of exposure to the nanofibers containing a low concentration of GNR-Quer.

Gold Nanocomplex Strongly Modulates the PI3K/Akt Pathway and Other Pathways in MCF-7 Breast Cancer Cell Line.

Conjugating drugs with gold nanoparticles (GNP) is a key strategy in cancer therapy. Herein, the potential inhibition of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, and other pathways of the MCF-7 cell-line, was investigated upon treatment with gold nanorods (GNR) conjugated with a PI3K inhibitor drug. The results revealed that the coupling of GNR with the drug drastically modulated the expression of PI3Kα at the gene and protein levels compared to the drug or GNR alone. The PI3Kα pathway is involved in tumor progression and development through the mediation of different mechanisms such as apoptosis, proliferation, and DNA damage. Treatment with the nanocomplex significantly affected the gene expression of several transcription factors responsible for cell growth and proliferation, apoptotic pathways, and cell cycle arrest. Furthermore, the gene expression of different regulatory proteins involved in cancer progression and immune responses were significantly modified upon treatment with the nanocomplex compared to the free drug or GNR alone.

Correction: Nanoparticle size and chemical modification play a crucial role in the interaction of nano gold with the brain: extent of accumulation and toxicity.

Correction for 'Nanoparticle size and chemical modification play a crucial role in the interaction of nano gold with the brain: extent of accumulation and toxicity' by Nouf N. Mahmoud et al., Biomater. Sci., 2020, DOI: 10.1039/c9bm02072a.

Nanoparticle size and chemical modification play a crucial role in the interaction of nano gold with the brain: extent of accumulation and toxicity.

The blood brain barrier (BBB) is a very selective barrier that protects the brain and the central nervous system (CNS) from the entry of harmful substances and helps regulate the exchange of different molecules and nutrients from and into the brain and the CNS. This selectivity makes delivering therapeutic and diagnostic materials across the BBB very challenging. In this study, different shapes and sizes of gold nanoparticles (GNP) were synthesized and functionalized with five different thiolated ligands to obtain GNP with various surface chemistries. The potential of GNP of different properties to be accumulated into the brain through the BBB and into other organs was investigated in a mouse model using qualitative and quantitative approaches. Gold nanorods (GNR) functionalized with 4-mercaptophenol (Mph) showed the highest penetration ability across the BBB into the brain with no significant deposition in other organs. Interestingly, increasing the size of GNR retarded their delivery into the brain, while enhancing their accumulation in other organs. On the other hand, gold nanospheres (GNS) demonstrated high deposition percentages in the brain and other organs with possible toxic effects. The properties of GNP play a crucial role in their interaction with the BBB and accumulation in the brain and other organs. Thus, GNP can be considered a promising nano-platform for drug delivery into the brain and as a photothermal-inducing agent against brain cancer.