School of Pharmacy, Shenyang Pharmaceutical University, China.
Department of Pharmacy, The Fourth Affiliated Hospital of China Medical University, China.
Biomaterials. 2022 Jul;286:121567. doi: 10.1016/j.biomaterials.2022.121567. Epub 2022 May 7.
The intracellular delivery of proteins is of great significance. For diseases such as cancer, heart disease and neurodegenerative diseases, many important pharmacological targets are located inside cells. For genetic engineering and cell engineering, various functional proteins need to be delivered into cells for gene editing or cell state regulation. However, most existing protein delivery strategies involve endosomal escape (endocytosis-dependent), resulting in inefficient delivery due to endosome trapping. In contrast, endocytosis-independent intracellular delivery, which refers to the directly delivery of proteins across the cell membrane to the cytoplasm, will bypass the low efficiency of early endosomal escape, avoid protein inactivation caused by late endosome/lysosome, fundamentally improve the intracellular delivery efficiency, and open up a new way for intracellular protein delivery. In this review, the latest advances in direct intracellular delivery of proteins through membrane perforation, membrane translocation, and membrane fusion were summarized. The mechanisms, related materials and potential therapeutic in living cells/in vivo for each approach were discussed in detail, and the future development in this promising field was briefly presented.
蛋白质的细胞内递送具有重要意义。对于癌症、心脏病和神经退行性疾病等疾病，许多重要的药理学靶点都位于细胞内部。对于基因工程和细胞工程，需要将各种功能蛋白递送到细胞内进行基因编辑或细胞状态调节。然而，大多数现有的蛋白质递送策略都涉及内涵体逃逸（依赖内吞作用），由于内涵体捕获，导致递送效率低下。相比之下，非内吞体依赖性的细胞内递送是指将蛋白质直接穿过细胞膜递送到细胞质中，这将绕过早期内涵体逃逸的低效率，避免由晚期内涵体/溶酶体引起的蛋白质失活，从根本上提高细胞内的递送效率，并为细胞内蛋白质的递送开辟了新途径。在这篇综述中，总结了通过膜穿孔、膜转位和膜融合直接进行细胞内蛋白质递送的最新进展。详细讨论了每种方法在活细胞/体内的机制、相关材料和潜在的治疗用途，并简要介绍了该有前途的领域的未来发展。
