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Microfluidics cell encapsulation offers a way to mimic a 3D microenvironment that supports cell growth and proliferation, while also protecting cells from environmental stress. This technique has found extensive applications in tissue engineering and cell therapies. Several studies have demonstrated the advantages of graphene oxide (GO) as an osteogenic inducer; however, the significance of GO on stem cell fate in the single-cell state is still unclear. Here, a microfluidics-based approach is developed for continuous encapsulation of mesenchymal stem cells (MSCs) at the single-cell level using alginate microgels. So, single-layer graphene oxide (slGO) nanosheet is used to be encapsulated inside the alginate droplets. The results of AFM and SEM show that slGO can increase the roughness and reduce the stiffness of alginate hydrogels. The Young's modulus of the alginate and alginate-slGO was obtained as 1414 kPa and 985.9 kPa, respectively. Live/dead assay and fluorescence microscopy images illustrate that slGO can maintain the viability and proliferation of microencapsulated hBMSCs. The obtained results show that slGO increases the mineralization of the encapsulated hBMSCs, so that microgels containing hBMSCs gradually became opaque during 21 days of culture. RT-qPCR results indicate that the expression of OCN, Runx2, and ALP in the alginate-slGO microgels is significantly higher than in the alginate microgels. The expression of OCN and Runx2 in the alginate-slGO microgels is 4.27 and 5.87-fold higher than in the alginate microgels, respectively. It can be concluded that low doses of slGO nanosheets have the potential to be utilized in the development of tissue engineering and bone regeneration. This finding offers a new method for creating injectable tissue transplants that are minimally invasive. [ABSTRACT FROM AUTHOR]

Background: Drug combination therapy is preferred over monotherapy in clinical research to improve therapeutic effects. Developing a new nanodelivery system for cancer drugs can reduce side effects and provide several advantages, including matched pharmacokinetics and potential synergistic activity. This study aimed to examine and determine the efficiency of the gemini surfactants (GSs) as a pH-sensitive polymeric carrier and cell-penetrating agent in cancer cells to achieve dual drug delivery and synergistic effects of curcumin (Cur) combined with tamoxifen citrate (TMX) in the treatment of MCF-7 and MDA-MB-231 human BC cell lines. Methods: The synthesized NPs were self-assembled using a modified nanoprecipitation method. The functional groups and crystalline form of the nanoformulation were examined by Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and dynamic light scattering (DLS) used to assess zeta potential and particle size, and the morphological analysis determined by transmission electron microscopy (TEM). The anticancer effect was evaluated through an in vitro cytotoxicity MTT assay, flow cytometry analysis, and apoptosis analysis performed for mechanism investigation. Results: The tailored NPs were developed with a size of 252.3 ± 24.6 nm and zeta potential of 18.2 ± 4.4 mV capable of crossing the membrane of cancer cells. The drug loading and release efficacy assessment showed that the loading of TMX and Cur were 93.84% ± 1.95% and 90.18% ± 0.56%, respectively. In addition, the drug release was more controlled and slower than the free state. Polymeric nanocarriers improved controlled drug release 72.19 ± 2.72% of Tmx and 55.50 ± 2.86% of Cur were released from the Tmx-Cur-Gs NPs after 72 h at pH = 5.5. This confirms the positive effect of polymeric nanocarriers on the controlled drug release mechanism. moreover, the toxicity test showed that combination-drug delivery was much more greater than single-drug delivery in MCF-7 and MDA-MB-231 cell lines. Cellular imaging showed excellent internalization of TMX-Cur-GS NPs in both MCF-7 and MDA-MB-231 cells and synergistic anticancer effects, with combination indices of 0.561 and 0.353, respectively. Conclusion: The combined drug delivery system had a greater toxic effect on cell lines than single-drug delivery. The synergistic effect of TMX and Cur with decreasing inhibitory concentrations could be a more promising system for BC-targeted therapy using GS NPs. [ABSTRACT FROM AUTHOR]

'Active targeting' refers to modifying a nanocarrier's surface with targeting ligands. This study introduced an efficient approach for immobilizing imidazole-based drugs onto the metallated-porphyrin complex within the porphysome nanocarrier. To enhance cellular and bacterial uptake, a Ni-porphyrin with a fatty acid tail was synthesized and placed in the bilayer center of DPPC, facilitating receptor-mediated endocytosis. The Ni-porphyrin in the head group of the Ni-porphyrin-tail was placed superficially in the polar region of the membrane. Spherical unilamellar vesicle formation (DPPC: Ni-porphyrin-tail 4:1 mole ratio), as metallo-porphysome, was achieved through supramolecular self-assembly in an aqueous buffer. These vesicles exhibited a diameter of 279 ± 7 nm and a zeta potential of −15.3 ± 2.5 mV, showcasing their unique cytocompatibility. Nitroimidazole was decorated on the surface of metallo-porphysomes and pistachio green hull extract (PGHE) was loaded into the carrier for synergistic activity against (E. coli) and (S. aureus) bacteria strains. The physicochemical properties of Nitroimidazole-porphysome-PGHE, including size, zeta potential, morphology, loading efficiency, and release profile under various pH and temperature conditions in simulated gastrointestinal fluids were characterized. This combination therapy prevented bacterial cell attachment and biofilm formation in Caco-2 cells, as colon epithelial cells. The remarkable benefit of this system is that it does not affect cell viability even at 0.5 mg/ml. This study demonstrates the potential of a new co-delivery system using biocompatible metallo-porphysomes to decrease bacterial infections. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the antioxidant and anti‐inflammatory effects of glucosamine nanoparticles (GNPs) grafted with gallic acid (GNPs‐g‐GA). Glucosamine hydrochloride (G‐HCl) was produced from shrimp shell, and then GNPs synthesized using ionic gelation method. GNPs‐g‐GA was prepared by coupling GNPs with GA via 1‐ethy‐3‐(3‐dimethylaminopropyl)‐carbodiimide (EDC) in combination with N‐hydroxysuccinimide (NHS) cross‐linking agents. The results indicated that the grafting of GA onto GNPs at different ratios increased the average size of the nanoparticles from 195.7 to 294.2 nm with various grafting degrees ranging from 73.3 to 146.4 mg GA/g GNPs‐g‐GA. The SEM images revealed the formation of spherical‐shaped GNPs‐g‐GA nanoparticles with approximate sizes ranging from 275.3 to 303.6 nm. The appearance of characteristic signals in the FT‐IR (C=C, C–O/C–C, and NH2) and 1H‐NMR (H‐2 and H‐6 at 6.95 ppm) spectra and the red shift in UV‐Vis spectrum provided further support of GNPs‐g‐GA successful synthesis. DPPH radical scavenging (from 20.0 to 70.4%) and ABTS radical scavenging (from 18.7 to 79.0%) activities and reducing power (nearly fivefold) sharply improved in GNPs‐g‐GA. Moreover, GNPs‐g‐GA was found nontoxic and drastically reduced the level of nitric oxide release and downregulated the synthesis of TNF‐α, IL‐1β, and IL‐6 in LPS‐induced RAW2647 murine macrophage cells through NF‐κB and MAPKs signaling pathways. Overall, these results suggested that the grafting of GNPs and GA is an effective strategy for the suppression of inflammation response and oxidation reaction in osteoarthritis. [ABSTRACT FROM AUTHOR]

In this study, an on–off–on fluorescence probe is developed for rapid, sensitive, and selective detection of Cu2+ ions and glutathione (GSH) based on green light-emitting insulin-capped gold nanoclusters (Ins/Au-NCs). Ins/Au-NCs with low toxicity and excellent stability were prepared by utilizing a simple and green strategy. Cu2+ ions can selectively decrease the fluorescence intensity of Ins/Au-NCs by an aggregation-caused quenching mechanism, which can be recovered in the presence of GSH. Under the optimized condition, the detection limits for determination of Cu2+ ions and GSH are estimated as 7.5 and 9.2 nM, with linear ranges of 0.05 to 1.7 μM and 0.05 to 1.5 μM, respectively. Chemical modeling was also employed to investigate the interaction of the Ins/Au-NCs probe with Cu2+, Hg2+, glutathione, and cysteine. The calculated molecular orbital energy well confirmed the experimental selective results obtained. Luminescence cellular imaging exhibited a sensitive response of the Ins/Au-NCs probe toward Cu2+ ions in breast cancer cells MCF-7, and thus, it potentially acted as an intracellular GSH probe in MCF-7 compared to the human fibroblast HFF cells. The as-prepared probe was successfully applied to low levels of Cu2+ ions and GSH in water and human serum samples. The designed Ins/Au-NCs-based probe may also provide a biocompatible platform for label-free GSH detection in biological and clinical implications that comprise staining and early prevention of cancer, AIDS, and Alzheimer's and cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa is the most common pathogen that causes chronic lung infections and recurrence of the disease in cystic fibrosis patients by hiding inside cells and biofilm matrix. Herein, we developed gentamicin and curcumin-loaded lipid-polymer hybrid nanoparticle- (termed CG-HNPs) to evaluate in vitro activities against biofilm-embedded P. aeruginosa and compared with lipid nanoparticles containing the same drugs (CG-Lip). The nanoparticles were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), fluorescence spectroscopy, and ultraviolet-visible (UV-vis) spectroscopy, which demonstrated that HNPs with a diameter of approximately 340 nm were uniform. The optimal CG-HNPs formulation illustrated high encapsulation (∼70%) and controlled release characteristics (gradually released in 72 h). The antibacterial activities of generated nanoparticles are maintained against planktonic and biofilm bacteria and it is effective in damage established biofilms. Besides, HNPs were biocompatible and nontoxic to J774 and HFF cell lines and uptake by the macrophages (J774), which facilitated the killing of intracellular bacteria in macrophages. These results introduced CG-HNPs as a promising antibacterial agent for the treatment of chronic infections and intracellular bacteria due to excellent antibacterial activity. [ABSTRACT FROM AUTHOR]

The evolution of sophisticated nanosystems has revolutionized biomedicine, notably in treating neurodegenerative diseases and cancer. These systems show potential in delivering medication precisely to affected tissues, improving treatment effectiveness while minimizing side effects. Nevertheless, a major hurdle in targeted drug delivery is breaching the blood-brain barrier (BBB), a selective shield separating the bloodstream from the brain and spinal cord. The tight junctions between endothelial cells in brain capillaries create a formidable physical barrier, alongside efflux transporters that expel harmful molecules. This presents a notable challenge for brain drug delivery. Nanosystems present distinct advantages in overcoming BBB challenges, offering enhanced drug efficacy, reduced side effects, improved stability, and controlled release. Despite their promise, challenges persist, such as the BBB's regional variability hindering uniform drug distribution. Efflux transporters can also limit therapeutic agent efficacy, while nanosystem toxicity necessitates rigorous safety evaluations. Understanding the long-term impact of nanomaterials on the brain remains crucial. Additionally, addressing nanosystem scalability, cost-effectiveness, and safety profiles is vital for widespread clinical implementation. This review delves into the advancements and obstacles of advanced nanosystems in targeted drug delivery for neurodegenerative diseases and cancer therapy, with a focus on overcoming the BBB., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: This study aimed to present the synthesis and characterization of four novel analogs of cyclophosphamide (2, 3, 4, 7) and their related precursors (1, 5, 6) and assess their anticancer activity against breast cancerous (MCF-7) and normal (HUVEC) cells., Method: Notably, 2-(bis(2-chloroethyl)amino)-1,3,2-diazaphospholidine 2-oxide ((2)) and 2-(bis(2-hydroxyethyl)amino)-1,3,2-diazaphospholidine 2-oxide ((7)) exhibited concentration- dependent cytotoxicity against the MCF-7 cell line, with IC50 values of 8.98 and 28.74 μM, respectively., Result: Annexin V/PI staining and ROS assays demonstrated reduced cell viability and mitochondrial dysfunction. in silico studies involving DFT-D optimization and Molegro virtual docking against B-DNA dodecamer and STAT3 receptors revealed enhanced interactions for certain compounds compared to cyclophosphamide., Conclusion: Importantly, the in silico and in vitro results corroborated each other, supporting the potential anticancer efficacy of these novel analogs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Wounds and the healing process are one of the main concerns of medical science today. A wound is any loss of integrity, or rupture of the layers of skin (epidermis, dermis, and hypodermis) or subcutaneous tissue caused by physical factors (surgical incision, trauma, pressure, and gunshot wounds) or chemical factors (acid burns). It is observed that soft tissue, muscle, or bone is involved in occurrences of wounds. Lesions and fractures of the skin surface necessitate medical attention, wherein dressings expedite the healing process by establishing a physical barrier between the wound and the external environment, thereby preventing further injury or infection. Hydrogel dressings create a moist environment that facilitates common healing steps, such as granulation hyperplasia, epidermal repair, and removal of excess dead tissue. The limited adhesion of the hydrogel and the hydrated wound bed allows for easy removal of the dressing without secondary damage, thereby significantly reducing the discomfort and risk of infection during dressing changes. These modern, wet dressings foster a moist healing environment by absorbing excess inflammatory secretions and allowing proper passage of steam and air, which expedites the healing process. In this analysis, the utilization of hydrogels as wound dressings is briefly presented.

Pseudomonas aeruginosa is the most common pathogen that causes chronic lung infections and recurrence of the disease in cystic fibrosis patients by hiding inside cells and biofilm matrix. Herein, we developed gentamicin and curcumin-loaded lipid-polymer hybrid nanoparticle- (termed CG-HNPs) to evaluate in vitro activities against biofilm-embedded P. aeruginosa and compared with lipid nanoparticles containing the same drugs (CG-Lip). The nanoparticles were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), fluorescence spectroscopy, and ultraviolet-visible (UV-vis) spectroscopy, which demonstrated that HNPs with a diameter of approximately 340 nm were uniform. The optimal CG-HNPs formulation illustrated high encapsulation (∼70%) and controlled release characteristics (gradually released in 72 h). The antibacterial activities of generated nanoparticles are maintained against planktonic and biofilm bacteria and it is effective in damage established biofilms. Besides, HNPs were biocompatible and nontoxic to J774 and HFF cell lines and uptake by the macrophages (J774), which facilitated the killing of intracellular bacteria in macrophages. These results introduced CG-HNPs as a promising antibacterial agent for the treatment of chronic infections and intracellular bacteria due to excellent antibacterial activity.