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Nanotechnology has enhanced therapeutic outcomes through nanoparticle-mediated drug delivery, mitigating drug toxicity. In this study, we propose the synthesis and physicochemical characterization of poly(lactic-co-glycolic acid) (PLGA) nanoparticles coated with hybrid membranes derived from lung adenocarcinoma cells (A549) and T lymphocytes (Jurkat) for the encapsulation of cisplatin, a standard chemotherapy agent in lung cancer treatment. Membrane-free cisplatin-loaded nanoparticles (NPCisPt) were prepared by nanoprecipitation, and hybrid membrane coating (NPCisPt@memb) was achieved by sonication. Both formulations were physicochemically characterized by dynamic light scattering (DLS), zeta potential measurements, Fourier-transform infrared spectroscopy (FTIR), and transmission electron microscopy (TEM). Cellular uptake was assessed in A549, Calu-3 (lung cancer), and MRC-5 (lung fibroblast) cell lines by flow cytometry and confocal fluorescence microscopy. NPCisPt presented a mean diameter of 87 ± 3 nm and a zeta potential of −32 ± 5 mV. After membrane functionalization, NPCisPt@memb exhibited a diameter of 87 ± 1 nm and a zeta potential of −32 ± 1 mV. The coating of nanoparticles was suggested by infrared spectroscopy, showing characteristic protein bands and transmission electron microscopy. Drug-containing and functionalized nanoparticles showed increased internalization in homologous tumor cells compared to fibroblast cells and other type cancer cells, suggesting homotypic recognition of the system. These findings support the potential of biomimetic nanoparticles as a promising platform for targeted cisplatin delivery in lung cancer, with prospects for enhanced therapeutic efficacy and reduced adverse effects.
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