将肿瘤相关巨噬细胞 (TAM) 复极化为肿瘤抑制性 M1 巨噬细胞被认为是增强癌症免疫治疗的一种有前景的策略。然而，一些免疫抑制配体（例如 LSECtin）仍然可以在 M1 巨噬细胞上高表达，导致治疗结果不令人满意。我们在此开发了一种抗体修饰的纳米平台，由聚乙二醇化氧化铁纳米颗粒（IONP）和通过腙键缀合到 IONP 表面的 LSECtin 抗体组成，用于增强癌症免疫治疗。静脉注射后，肿瘤微环境（TME）pH值可以触发腙键断裂并诱导纳米平台解离成游离的LSECtin抗体和IONP。因此，IONP 可以将 TAM 重新极化为 M1 巨噬细胞，从而重塑免疫抑制性 TME，并通过分泌肿瘤因子（例如白细胞介素 12）提供额外的抗癌作用。同时，LSECtin抗体可以进一步阻断M1巨噬细胞表达的LSECtin活性，解除其对CD8 T细胞的免疫抑制作用，最终显着抑制肿瘤生长。

Repolarizing tumor-associated macrophages (TAMs) into tumor-inhibiting M1 macrophages has been considered a promising strategy for enhanced cancer immunotherapy. However, several immunosuppressive ligands (e.g., LSECtin) can still be highly expressed on M1 macrophages, inducing unsatisfactory therapeutic outcomes. We herein developed an antibody-decorated nanoplatform composed of PEGylated iron oxide nanoparticles (IONPs) and LSECtin antibody conjugated onto the surface of IONPs via the hydrazone bond for enhanced cancer immunotherapy. After intravenous administration, the tumor microenvironment (TME) pH could trigger the hydrazone bond breakage and induce the disassociation of the nanoplatform into free LSECtin antibodies and IONPs. Consequently, the IONPs could repolarize TAMs into M1 macrophages to remodel immunosuppressive TME and provide an additional anticancer effect via secreting tumoricidal factors (e.g., interlukin-12). Meanwhile, the LSECtin antibody could further block the activity of LSECtin expressed on M1 macrophages and relieve its immunosuppressive effect on CD8+ T cells, ultimately leading to significant inhibition of tumor growth.