人工细胞由合成材料构建，以模拟自然细胞的生物功能。借助纳米工程技术，设计用于类似生物的功能的人工细胞成为替代自然细胞的选择，并展现了在生物医学应用领域广泛的潜力。尤其在癌症治疗中，免疫活化巨噬细胞的缺乏导致肿瘤进展和免疫耐药性。为了克服这一局限性，我们构建了一种BaSO4@ZIF-8/转铁蛋白（TRF）纳米巨噬细胞（NMΦ），作为免疫活化巨噬细胞的替代方案。与自然免疫活化巨噬细胞相似，NMΦ通过TRF对肿瘤细胞的特异亲和力在肿瘤内稳定滞留。然后，在肿瘤微环境下，ZIF-8层中释放出作为“人工细胞因子”的Zn2+。类似于促炎细胞因子，Zn2+能够触发细胞各别，暴露出肿瘤抗原，而被BaSO4空腔有选择性地捕获。因此，NMΦ的分级纳米结构使其能够介导肿瘤细胞的免疫原性死亡，并随后通过抗原捕获激活T细胞，以形成长期的抗肿瘤免疫。作为概念验证，NMΦ模拟了巨噬细胞的生物功能，包括肿瘤滞留、细胞因子释放、抗原捕获和免疫活化，有望为人工细胞的设计和生物医学应用提供范例。© 2023. 上海交通大学。

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.© 2023. Shanghai Jiao Tong University.