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Cellular membranes and endocytic uptake pathways represent the fundamental biological structures and processes through which cells internalize extracellular substances, ranging from small nutrients to large macromolecules and pathogens (Alberts et al., Molecular Biology of the Cell, 2014). The plasma membrane acts as a selective barrier, while various endocytic routes—including clathrin-mediated endocytosis, caveolae-mediated endocytosis, and macropinocytosis—facilitate the transport of materials into the endolysosomal system (Sahay et al., Nature Nanotechnology, 2010). In drug development, these pathways are not typically targeted for inhibition but are instead exploited for the delivery of complex therapeutics such as nucleic acids in lipid nanoparticles or antibody-drug conjugates (Behzadi et al., Chemical Society Reviews, 2017). Many viruses and bacteria also hijack these pathways to gain entry into recipient cells, making the study of these mechanisms vital for infectious disease research (Marsh & Helenius, Cell, 2006). Therapeutic challenges include ensuring the cargo escapes the endosome before lysosomal degradation and achieving cell-type specificity to avoid systemic toxicity (Kou et al., African Journal of Pharmacy and Pharmacology, 2013). Overall, these pathways are central to the pharmacokinetics of intracellularly acting drugs and the pathophysiology of many infections.
Facilitation of intracellular delivery via vesicle-mediated internalization (e.g., clathrin-mediated endocytosis) followed by endosomal escape to reach the cytosol (Sahay et al., Nature Nanotechnology, 2010).
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