Advanced Strategies for Overcoming Endosomal/Lysosomal Barrier in Nanodrug Delivery

• Published in: Research (Washington) Vol. 6; p. 0148
• Main Authors: Qiu, Chong, Xia, Fei, Zhang, Junzhe, Shi, Qiaoli, Meng, Yuqing, Wang, Chen, Pang, Huanhuan, Gu, Liwei, Xu, Chengchao, Guo, Qiuyan, Wang, Jigang
• Format: Journal Article
• Language: English
• Published: United States AAAS 2023; American Association for the Advancement of Science (AAAS)
• Subjects: Review
• ISSN: 2639-5274; 2639-5274
• DOI: 10.34133/research.0148

Nanocarriers have therapeutic potential to facilitate drug delivery, including biological agents, small-molecule 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.