Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, People's Republic of China.
School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, Anhui 230026, People's Republic of China.
ACS Nano. 2021 Dec 28;15(12):19298-19309. doi: 10.1021/acsnano.1c05392. Epub 2021 Nov 16.
Tumor-associated macrophages (TAMs) that infiltrate in most tumor tissues are closely correlated with proliferation and metastasis of tumor cells. Immunomodulation of TAMs from pro-tumorigenic M2 phenotype to anti-tumorigenic M1 phenotype is crucial for oncotherapy. Herein, an iron nanotrap was utilized to remodel TAMs for tumor growth inhibition. In the formulation, the ultrasmall nanotrap could capture and targetedly transport endogenous iron into TAMs even inside the tumor. Upon exposing to the lysosomal acidic conditions and intracellular HO, iron was released from the nanotrap and produced the generation of oxidative stress, which could reprogram TAMs. The activated M1 macrophages could induce immune responses and suppress tumor growth ultimately. Meanwhile, this metal-free nanotrap with degradability by HO possessed favorable biocompatibility. Our work would present potential opportunities of utilizing endogenous substances for secure treatment of various diseases.
肿瘤相关巨噬细胞(TAMs)浸润在大多数肿瘤组织中,与肿瘤细胞的增殖和转移密切相关。将 TAMs 从促肿瘤发生的 M2 表型免疫调节为抗肿瘤发生的 M1 表型,对于肿瘤治疗至关重要。在此,利用铁纳米陷阱重塑 TAMs 以抑制肿瘤生长。在配方中,超小的纳米陷阱可以捕获并靶向将内源性铁转运到 TAMs 中,甚至在肿瘤内部。当暴露于溶酶体酸性条件和细胞内的 HO 时,铁从纳米陷阱中释放出来,并产生氧化应激,从而重编程 TAMs。激活的 M1 巨噬细胞可以引发免疫反应并最终抑制肿瘤生长。同时,这种具有 HO 降解能力的无金属纳米陷阱具有良好的生物相容性。我们的工作将为利用内源性物质安全治疗各种疾病提供潜在的机会。