Artificial Macrophage with Hierarchical Nanostructure for Biomimetic Reconstruction of Antitumor Immunity

Henan Zhao; Renyu Liu; Liqiang Wang; Feiying Tang; Wansong Chen; You-Nian Liu

doi:10.1007/s40820-023-01193-4

Artificial Macrophage with Hierarchical Nanostructure for Biomimetic Reconstruction of Antitumor Immunity

Nanomicro Lett. 2023 Sep 22;15(1):216. doi: 10.1007/s40820-023-01193-4.

Authors

Henan Zhao¹, Renyu Liu², Liqiang Wang³, Feiying Tang⁴, Wansong Chen⁵, You-Nian Liu⁶

Affiliations

¹ Hunan Provincial Key Laboratory of Micro & Nano Materials Interface Science, College of Chemistry and Chemical Engineering, Central South University, Changsha, 410083, Hunan, People's Republic of China.
² Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People's Republic of China.
³ Henan Province Industrial Technology Research Institute of Resources and Materials, School of Material Science and Engineering, Zhengzhou University, Zhengzhou, 450001, Henan, People's Republic of China.
⁴ College of Chemical Engineering, Xiangtan University, Xiangtan, 411105, Hunan, People's Republic of China.
⁵ Hunan Provincial Key Laboratory of Micro & Nano Materials Interface Science, College of Chemistry and Chemical Engineering, Central South University, Changsha, 410083, Hunan, People's Republic of China. chenws@csu.edu.cn.
⁶ Hunan Provincial Key Laboratory of Micro & Nano Materials Interface Science, College of Chemistry and Chemical Engineering, Central South University, Changsha, 410083, Hunan, People's Republic of China. liuyounian@csu.edu.cn.

Abstract

Artificial cells are constructed from synthetic materials to imitate the biological functions of natural cells. By virtue of nanoengineering techniques, artificial cells with designed biomimetic functions provide alternatives to natural cells, showing vast potential for biomedical applications. Especially in cancer treatment, the deficiency of immunoactive macrophages results in tumor progression and immune resistance. To overcome the limitation, a BaSO₄@ZIF-8/transferrin (TRF) nanomacrophage (NMΦ) is herein constructed as an alternative to immunoactive macrophages. Alike to natural immunoactive macrophages, NMΦ is stably retained in tumors through the specific affinity of TRF to tumor cells. Zn²⁺ as an "artificial cytokine" is then released from the ZIF-8 layer of NMΦ under tumor microenvironment. Similar as proinflammatory cytokines, Zn²⁺ can trigger cell anoikis to expose tumor antigens, which are selectively captured by the BaSO₄ cavities. Therefore, the hierarchical nanostructure of NMΦs allows them to mediate immunogenic death of tumor cells and subsequent antigen capture for T cell activation to fabricate long-term antitumor immunity. As a proof-of-concept, the NMΦ mimics the biological functions of macrophage, including tumor residence, cytokine release, antigen capture and immune activation, which is hopeful to provide a paradigm for the design and biomedical applications of artificial cells.

Keywords: Anoikis; Antitumor immunotherapy; Artificial macrophage; Chemical messenger; Hierarchical nanostructure.