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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]