Artificial Assembled Macrophage Co-Deliver Black Phosphorus Quantum Dot and CDK4/6 Inhibitor for Colorectal Cancer Triple-Therapy

人工组装巨噬细胞共同递送黑磷量子点和CDK4/6抑制剂用于结直肠癌三联疗法

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作者:Yuxiao Fang, Zipeng Zhang, Yang Liu, Tong Gao, Shuang Liang, Qihui Chu, Li Guan, Weiwei Mu, Shunli Fu, Huizhen Yang, Na Zhang, Yongjun Liu

Abstract

In recent years, therapeutic strategies based on macrophages have been inspiringly developed, but due to the high intricacy and immunosuppression of the tumor microenvironment, the widespread use of these strategies still faces significant challenges. Herein, an artificial assembled macrophage concept (AB@LM) was presented to imitate the main antitumor abilities of macrophages of tumor targeting, promoting the antitumor immunity, and direct tumor-killing effects. The artificial assembled macrophage (AB@LM) was prepared through an extrusion method, which is to fuse the macrophage membrane with abemaciclib and black phosphorus quantum dot (BPQD)-loaded liposomes. AB@LM showed good stability and tumor targeting ability with the help of macrophage membrane. Furthermore, AB@LM reversed the immunosuppressive tumor microenvironment by inhibiting regulatory T cells (Tregs) and stimulating the maturation of antigen-presenting cells to activate the antitumor immune response through triggering an immunogenic cell death effect. More importantly, in the colorectal tumor model in vivo, a strong cooperative therapeutic effect of photo/chemo/immunotherapy was observed with high tumor inhibition rate (95.3 ± 2.05%). In conclusion, AB@LM exhibits excellent antitumor efficacy by intelligently mimicking the abilities of macrophages. A promising therapeutic strategy for tumor treatment based on imitating macrophages was provided in this study.

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