Targeted endocytosis: Strategies in drug delivery systems for enhancing antitumor efficacy.

Endocytosis represents a critical mechanism for the cellular entry of many drug delivery systems, enabling them to exert their therapeutic actions. While advances in targeted therapy and immunotherapy have markedly improved survival rates for cancer patients, inefficient drug delivery continues to pose a major limitation to drug efficacy. In response, recent research has increasingly focused on designing drug delivery platforms that exploit endocytic pathways. Such systems aim to modulate how tumor cells internalize therapeutics, thereby optimizing drug transport into cells, overcoming resistance mechanisms, and improving antitumor outcomes. However, alterations in endocytic pathways within tumor cells can significantly influence treatment efficacy. This review explores the distinct mechanisms of endocytosis dysregulated in cancers and highlights how strategic targeting of these pathways could help alleviate delivery challenges, promote intracellular drug accumulation, and circumvent resistance. We also examine the primary mechanisms governing drug internalization and summarize key strategies and applications of endocytosis-targeted drug delivery in oncology. Finally, we discuss current limitations in the field and offer perspectives on future developments.