Advanced Strategies for Overcoming Endosomal/Lysosomal Barrier in Nanodrug Delivery

Nanocarriers have therapeutic potential to facilitate drug delivery, including biological agents, smallmolecule drugs, and nucleic acids. However, their efficiency is limited by several factors; among which, endosomal/lysosomal degradation after endocytosis is the most important. This review summarizes advanced strategies for overcoming endosomal/lysosomal barriers to efficient nanodrug delivery based on the perspective of cellular uptake and intracellular transport mechanisms. These strategies include promoting endosomal/lysosomal escape, using non-endocytic methods of delivery to directly cross the cell membrane to evade endosomes/lysosomes and making a detour pathway to evade endosomes/ lysosomes. On the basis of the findings of this review, we proposed several promising strategies for overcoming endosomal/lysosomal barriers through the smarter and more efficient design of nanodrug delivery systems for future clinical applications.

Automated summary

Nanocarriers have therapeutic potential for drug delivery, but their efficiency is limited by endosomal/lysosomal degradation. This review summarizes advanced strategies for overcoming this barrier, including promoting endosomal/lysosomal escape, using non-endocytic delivery methods, and taking a detour pathway. Several promising strategies are proposed for smarter and more efficient nanodrug delivery systems.