The mechanism of lauric acid-modified protein nanocapsules escape from intercellular trafficking vesicles and its implication for drug delivery

Drug Delivery

Qianwei Miao¹  Xinyu Ye¹  Xiuli Chen¹  Lijuan Jiang¹  Xudong Zhang²  Gan Liu³  Yun Zhou³  Lin Mei³  Xin Liang³  Li Gao⁴ 

[1] School of Life Sciences, Tsinghua University, Beijing, PR China;School of Life Sciences, Tsinghua University, Beijing, PR China;Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC, US;School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou, PR China;The Affiliated Hospital of Guilin Medical College, Guilin, PR China;

关键词: Lauric acid;    protein nanocapsules;    endocytosis;    autophagy;    drug delivery;   

DOI  :  10.1080/10717544.2018.1461954

来源: publisher

【 摘 要 】

Protein nanocapsules have exhibited promising potential applications in the field of protein drug delivery. A major issue with various promising nano-sized biotherapeutics including protein nanocapsules is that owing to their particle size they are subject to cellular uptake via endocytosis, and become entrapped and then degraded within endolysosomes, which can significantly impair their therapeutic efficacy. In addition, many nano-sized biotherapeutics could be also sequestered by autophagosomes and degraded through the autolysosomal pathway. Thus, a limiting step in achieving an effective protein therapy is to facilitate the endosomal escape and auto-lysosomal escape to ensure cytosolic delivery of the protein drugs. Here, we prepared a protein nanocapsule based on BSA (nBSA) and the BSA nanocapsules modified with a bilayer of lauric acid (LA-nBSA) to investigate the escape effects from the endosome and autophagosome. The size distribution of nBSA and LA-nBSA analyzed using DLS presents a uniform diameter centered at 10 nm and 16 nm. The data also showed that FITC-labeled nBSA and LA-nBSA were taken up by the cells mainly through Arf-6-dependent endocytosis and Rab34-mediated macropinocytosis. In addition, LA-nBSA could efficiently escape from endosomal before the degradation in endo-lysosomes. Autophagy could also sequester the LA-nBSA through p62 autophagosome vesicles. These two types of nanocapsules underwent different intracellular destinies and lauric acid (LA) coating played a vital role in intracellular particle retention. In conclusion, the protein nanocapsules modified with LA could enhance the protein nanocapsules escape from intercellular trafficking vesicles, and protect the protein from degradation by the lysosomes.

【 授权许可】

CC BY