Engineering of HN3 increases the tumor targeting specificity of exosomes and upgrade the anti-tumor effect of sorafenib on HuH-7 cells

PeerJ

article

Cong He¹  Doulathunnisa Jaffar Ali¹  Yumin Li¹  Yanliang Zhu¹  Bo Sun¹  Zhongdang Xiao¹ 

[1] State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University;Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University

关键词: Exosomes;    GPC3;    HN3;    HuH-7;    HEK-293;    Sorafenib;   

DOI  :  10.7717/peerj.9524

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

Safe, efficient and cancer cell targeted delivery of CRISPR/Cas9 is important to increase the effectiveness of available cancer treatments. Although cancer derived exosomes offer significant advantages, the fact that it carries cancer related/inducing signaling molecules impedes them from being used as a reliable drug delivery vehicle. In this study, we report that normal epithelial cell-derived exosomes engineered to have HN3 (HN3LC9-293exo), target tumor cells as efficiently as that of the cancer cell-derived exosomes (C9HuH-7exo). HN3LC9-293exo were quickly absorbed by the recipient cancer cell in vitro. Anchoring HN3 to the membrane of the exosomes using LAMP2, made HN3LC9-293exo to specifically enter the GPC3+ HuH-7 cancer cells than the GPC3− LO2 cells in a co-culture model. Further, sgIQ 1.1 plasmids were loaded to exosomes and surprisingly, in combination with sorafenib, synergistic anti-proliferative and apoptotic effect of loaded HN3LC9-293exo was more than the loaded C9HuH-7exo. While cancer-derived exosomes might induce the drug resistance and tumor progression, normal HEK-293 cells-derived exosomes with modifications for precise cancer cell targeting like HN3LC9-293exo can act as better, safe and natural delivery systems to improve the efficacy of the cancer treatments.

【 授权许可】

CC BY