Bioengineered Macrophages Can Responsively Transform into Nanovesicles To Target Lung Metastasis

Nano Letters
Haiqiang CaoYaping Li

Abstract

Specific drug delivery to metastatic tumors remains a great challenge for antimetastasis therapy. We herein report a bioengineered macrophage-based delivery system (LD-MDS) that can be preferentially delivered to lung metastases and intelligently transformed into nanovesicles and secondary nanovesicles for antimetastasis therapy. LD-MDS was prepared by anchoring a legumain-specific propeptide of melittin (legM) and cytotoxic soravtansine (DM4) prodrug onto the membrane of living macrophages. LD-MDS is responsively activated by legumain protease and converted into DM4-loaded exosome-like nanovesicles (DENs), facilitating efficient internalization by metastatic 4T1 cancer cells and considerable cell death. Afterward, the damaged 4T1 cells can release secondary nanovesicles and free drug molecules to destroy neighboring cancer cells. In vivo, LD-MDS displays superior targeting efficiency for lung metastatic lesions with diameters less than 100 μm and remarkably inhibits lung metastasis. This study provides a new opportunity to explore endogenous macrophages as living drug delivery vehicles with controlled drug release to target metastatic lung tumors.

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Citations

Oct 1, 2019·Advanced Materials·Pengcheng ZhangYaping Li
Apr 8, 2020·Biomaterials Science·He DongRan Mo
Aug 29, 2020·Advanced Materials·Yuqiong XiaXiaoyuan Chen
Aug 21, 2019·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Jinfeng LiaoZhiyong Qian
Nov 24, 2020·Chemical Society Reviews·Guo-Feng LuoXian-Zheng Zhang
Mar 2, 2021·Advanced Materials·Xu ZhangHélder A Santos
Sep 6, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Weishuo LiCan Zhang
Apr 14, 2021·ACS Applied Materials & Interfaces·Jie ZhouHonglin Jin
Jul 30, 2021·Advanced Science·Yuezhou ZhangWei Huang

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