Cellular uptake pathways and intracellular cargo targets

Cellular uptake pathways and intracellular cargo targets refer to the collective biological mechanisms, such as endocytosis, phagocytosis, and pinocytosis, that cells use to internalize extracellular materials and route them to specific organelles (Nature Reviews Molecular Cell Biology, 2018). These pathways are fundamental to cellular homeostasis, nutrient acquisition, and the regulation of cell surface signaling receptors (Trends in Cell Biology, 2020). In the context of drug development, these pathways are not typically targeted for inhibition but are instead exploited as delivery routes for complex therapeutics, including antibody-drug conjugates (ADCs) and nucleic acid therapies (Journal of Controlled Release, 2021). By utilizing receptor-mediated endocytosis, drugs can be specifically internalized into target cells, such as tumor cells expressing high levels of a particular surface antigen (Nature Reviews Drug Discovery, 2022). Once internalized, the therapeutic cargo must navigate complex intracellular trafficking to reach its site of action, such as the cytosol or nucleus, while avoiding premature degradation in the lysosome. Dysregulation of these pathways is implicated in various pathologies, including viral infections that hijack endocytosis for entry and cancers that alter receptor recycling to promote growth (Cell, 2017).

Other names

EndocytosisIntracellular traffickingVesicular transportCellular internalizationEndocytic pathways

Exploitation of endogenous internalization mechanisms, such as receptor-mediated endocytosis, to facilitate the cellular entry and intracellular distribution of therapeutic payloads.