抗肿瘤 M1 样和促肿瘤 M2 样肿瘤相关巨噬细胞 (TAM) 在肿瘤微环境 (TME) 中共存。这些M1/M2亚群对肿瘤的不利影响直接影响目前提高抗肿瘤免疫反应的策略。因此，通过重编程TAM来改变肿瘤免疫抑制微环境引起了人们的广泛关注。在本文中，我们构建了靶向 M2 样 TAM 的仿生纳米颗粒 (HMMDN-Met@PM)，用于巨噬细胞重新极化。具体来说，仿生纳米颗粒的核心是负载二甲双胍的中空介孔二氧化锰纳米颗粒（HMMDN-Met）。得益于HMMDN的中空多孔结构，本工作中采用的M1/M2调节剂二甲双胍可以轻松、广泛地负载到HMMDN中。此外，利用巨噬细胞膜进行 HMMDN-Met 涂层 (HMMDN-Met@MM)，以防止药物过早渗漏并提供特定的分子识别/TME 靶向。此外，在巨噬细胞膜表面修饰M2巨噬细胞靶向肽（M2pep），将药物特异性递送至M2样TAM，促进M2巨噬细胞向M1巨噬细胞极化。通过体外和体内研究，我们发现M2型巨噬细胞的表面标志物和炎症因子CD206、Arg-1和IL-10的表达量下降，而M1型巨噬细胞的表面标志物和炎症因子CD80、 TNF-α和iNOS增加，表明M2巨噬细胞成功复极化，最终实现对肿瘤生长的抑制。同时，在肿瘤的酸性和GSH条件下，HMMDN分解为Mn2+，作为磁共振成像的造影剂，从而实现对肿瘤的追踪。这项工作将仿生纳米系统应用于靶向成像和免疫治疗，为肿瘤抑制策略设计铺平了道路。© 2023。作者。

Anti-tumor M1-like and pro-tumor M2-like tumor-associated macrophages (TAMs) coexist in tumor microenvironments (TME). The adverse effects of these M1/M2 subsets on tumors directly affect the current strategies to improve anti-tumor immune response. Therefore, it has attracted great attention to change the tumor immunosuppressive microenvironment by reprogramming TAMs. In this paper, we constructed biomimetic nanoparticles (HMMDN-Met@PM) targeting M2-like TAMs for macrophage re-polarization. In detail, the core of the biomimetic nanoparticles is metformin-loaded hollow mesoporous manganese dioxide nanoparticles (HMMDN-Met). Benefited from the hollow and porous structure of HMMDN, metformin, the regulator of M1/M2 adopted in this work, can be easily and widely loaded into HMMDN. Moreover, macrophage membranes were utilized for HMMDN-Met coating (HMMDN-Met@MM) to prevent the premature drug leakage and provide specific molecular recognition/TME targeting. In addition, M2 macrophage targeting peptide (M2pep) was modified on the surface of macrophage membrane to specifically deliver the drug to M2-like TAMs to promote the polarization of M2 to M1 macrophages. Through in vitro and in vivo studies, we found that the expression of surface markers and inflammatory factors CD206, Arg-1 and IL-10 of type M2 macrophages decreased, while the surface markers of type M1 macrophages and the expression of inflammatory factors CD80, TNF-α and iNOS increased, indicating the successful re-polarization of M2 macrophages and finally realizing the inhibition of tumor growth. At the same time, under the acidic and GSH conditions of tumor, HMMDN was decomposed into Mn2+, which is a contrast agent for magnetic resonance imaging, thus realizing the tracking of tumor. This work practices biomimetic nanosystem in targeted imaging and immunotherapy, paving the way for strategy designing for tumor inhibition.© 2023. The Author(s).