仿生纳米凝胶系统恢复巨噬细胞吞噬作用，用于磁共振成像引导的乳腺癌协同化学免疫治疗,Advanced Healthcare Materials

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仿生纳米凝胶系统恢复巨噬细胞吞噬作用，用于磁共振成像引导的乳腺癌协同化学免疫治疗
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2023-07-20 , DOI: 10.1002/adhm.202300967
Lulu Li ₁ , Yue Gao ₁ , Yiming Zhang ₁ , Rui Yang ₁ , Zhijun Ouyang ₁ , Rui Guo ₁ , Hongwei Yu ₂ , Xiangyang Shi ₁ , Xueyan Cao ₁

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仍有待开发促进肿瘤特异性药物输送和恢复免疫攻击的新策略，以克服目前化疗的局限性。据报道，癌细胞膜（CM）伪装和超小氧化铁纳米颗粒（USIO NP）负载的聚乙烯亚胺纳米凝胶（NG）系统可共同递送多西紫杉醇（DTX）和CD47 siRNA（siCD47）。所制备的共递送系统表现出良好的胶体稳定性、生物相容性和r ₁弛豫率（1.35 mM ^-1 s ^-1），并且能够在肿瘤微环境中氧化还原响应释放负载的DTX。NG系统实现DTX和siCD47同源靶向递送至小鼠乳腺癌细胞（4T1细胞），实现高效化疗和基因沉默；因此，通过下调癌细胞上的“别吃我”信号，诱导免疫原性细胞死亡（ICD）并恢复巨噬细胞的吞噬作用。同样，共递送系统还可以作用于巨噬细胞，促进其 M1 极化，这可以与 DTX 介导的 ICD 和抗体介导的免疫检查点阻断相结合，以产生用于稳健化学免疫治疗的效应 T 细胞。此外，USIO NPs 合并的 NG 系统还允许对肿瘤进行磁共振成像。所开发的仿生 NG 系统作用于癌细胞和巨噬细胞，在恢复巨噬细胞吞噬功能的化学免疫治疗方面具有广阔的前景。

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A Biomimetic Nanogel System Restores Macrophage Phagocytosis for Magnetic Resonance Imaging-Guided Synergistic Chemoimmunotherapy of Breast Cancer

Novel strategies to facilitate tumor-specific drug delivery and restore immune attacks remain to be developed to overcome the current limitations of chemotherapy. Herein, a cancer cell membrane (CM)-camouflaged and ultrasmall iron oxide nanoparticles (USIO NPs)-loaded polyethylenimine nanogel (NG) system is reported to co-deliver docetaxel (DTX) and CD47 siRNA (siCD47). The prepared co-delivery system exhibits good colloidal stability, biocompatibility, and r₁ relaxivity (1.35 mM^-1s⁻¹) and enables redox-responsive release of the loaded DTX in the tumor microenvironment. The NG system realizes homologous targeting delivery of DTX and siCD47 to murine breast cancer cells (4T1 cells) for efficient chemotherapy and gene silencing; thus, inducing immunogenic cell death (ICD) and restoring macrophage phagocytic effect through downregulation of “don't eat me” signals on cancer cells. Likewise, the co-delivery system can also act on macrophages to promote their M1 polarization, which can be combined with DTX-mediated ICD and antibody-mediated immune checkpoint blockade to generate effector T cells for robust chemoimmunotherapy. Further, the USIO NPs-incorporated NG system also allows for magnetic resonance imaging of tumors. The developed biomimetic NG system acting on both cancer cells and macrophages holds a promising potential for macrophage phagocytosis-restored chemoimmunotherapy.

更新日期：2023-07-20

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