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Cellular uptake via endocytosis and membrane fusion refers to the fundamental biological processes by which cells internalize extracellular materials, ranging from small molecules to large pathogens. Endocytosis is a form of active transport where the plasma membrane invaginates to capture substances in vesicles, a process categorized into pathways such as clathrin-mediated endocytosis, caveolae-mediated endocytosis, and macropinocytosis (NIH, 2022). Membrane fusion is the process by which two lipid bilayers merge into one, a mechanism essential for the entry of enveloped viruses like HIV-1 and SARS-CoV-2 into host cells (Nature Reviews Molecular Cell Biology, 2018). In modern pharmacology, these pathways are not typically defined as a single molecular target but are instead mechanisms exploited for the delivery of advanced therapeutics like lipid nanoparticles (LNPs) and antibody-drug conjugates (ADCs) (ScienceDirect, 2021). Successful drug delivery often requires the therapeutic agent to trigger endocytosis and subsequently escape the endosome to avoid degradation in the lysosome. Conversely, inhibiting these processes is a key strategy in antiviral therapy, where drugs like fusion inhibitors prevent the viral envelope from merging with the host cell membrane (PubMed, 2020). Understanding these pathways is critical for biotech analysts evaluating the efficacy and safety of intracellularly acting drugs.
Drugs either inhibit these processes to prevent viral entry or exploit them to deliver therapeutic cargo, such as nucleic acids or toxins, into the cytoplasm via vesicle formation or lipid bilayer merging.
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