Preparation of Bacillus-mimic liposomes destroying TAMs for the treatment of cancer.

Abstract

The enrichment rate of drugs in tumors seriously affects the effect of tumor treatment. Tumor-associated macrophages (TAMs) could penetrate deeply into the tumor and accumulate in hypoxic areas. Therefore, using TAMs to deliver drugs can effectively increase the enrichment rate. However, as immune cell, macrophages will clear the internal drugs and their antitumor activity. Mycobacterium tuberculosis (M. tuberculosis) can inhibit the decomposition ability of TAMs and stay stable in macrophages. Herein, we prepared a Bacillus-mimic liposome by embedding the fragments of M. tuberculosis into the liposome. In vitro experiments showed that it can stay stable in TAMs for at least 29 h without decomposing. Then, TAMs would burst as they gobble up materials and cannot digest them. Thus, the prepared liposome could "domesticate" TAMs and kill macrophages after they are used up, further destroy the tumor microenvironment, and finally kill the tumor. Cytotoxicity experiments confirmed that it has a certain killing effect on macrophages, tumor cells, and normal cells. In vivo tumor suppression experiments confirmed that it has the effect of inhibiting tumor growth.