Inhibiting collagen I production and tumor cell colonization in the lung via miR-29a-3p loading of exosome-/liposome-based nanovesicles

Acta Pharmaceutica Sinica B

Cancan Du¹  Zhihai Qin²  Wenqing Li³  Zhongyu Qin⁴  Ming Wang⁵  Zhuoyu Gu⁵  Ziming Jiang⁵  Yan Yan⁵  Xiaohan Yao⁵  Jiajia Wan⁵  Xixi Duan⁵  Longze Pan⁵  Fazhan Wang⁵ 

[1] Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450052, China;Corresponding authors. Tel./fax: [phone].;Changzhi Medical College, Changzhi 046000, China;Department of Urology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou 450052, China;Medical Research Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou 450052, China;

关键词: Lung metastasis;    miR-29a-3p;    Collagen I;    Liposomal nanovesicle;    Exosomes;    Fibroblasts;   

DOI  :  

来源: DOAJ

【 摘 要 】

The lung is one of the most common sites for cancer metastasis. Collagens in the lung provide a permissive microenvironment that supports the colonization and outgrowth of disseminated tumor cells. Therefore, down-regulating the production of collagens may contribute to the inhibition of lung metastasis. It has been suggested that miR-29 exhibits effective anti-fibrotic activity by negatively regulating the expression of collagens. Indeed, our clinical lung tumor data shows that miR-29a-3p expression negatively correlates with collagen I expression in lung tumors and positively correlates with patients’ outcomes. However, suitable carriers need to be selected to deliver this therapeutic miRNA to the lungs. In this study, we found that the chemotherapy drug cisplatin facilitated miR-29a-3p accumulation in the exosomes of lung tumor cells, and this type of exosomes exhibited a specific lung-targeting effect and promising collagen down-regulation. To scale up the preparation and simplify the delivery system, we designed a lung-targeting liposomal nanovesicle (by adjusting the molar ratio of DOTAP/cholesterol–miRNAs to 4:1) to carry miR-29a-3p and mimic the exosomes. This liposomal nanovesicle delivery system significantly down-regulated collagen I secretion by lung fibroblasts in vivo, thus alleviating the establishment of a pro-metastatic environment for circulating lung tumor cells.

【 授权许可】

Unknown