Pre-Induced ICD Membrane-Coated Carrier-Free Nanoparticles for the Personalized Lung Cancer Immunotherapy

预诱导ICD膜包覆无载体纳米粒子用于个性化肺癌免疫治疗

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作者:Shilin Li, Shasha Jiang, Muhammad Saif Ur Rahman, Jie Mei, Xinlian Wang, Jipeng Jiang, Yandong Chen, Shanshan Xu, Ying Liu

Abstract

Immunotherapy is a required adjuvant method in lung cancer therapy clinically. The single immune adjuvant failed to show the expected clinical therapeutic efficacy due to its rapid drug metabolism and inability to accumulate in the tumor site efficiently. Immunogenic cell death (ICD) is a new anti-tumor strategy combined with immune adjuvants. It can provide tumor-associated antigens, activate dendritic cells, and attract lymphoid T cells into the tumor microenvironment. Here doxorubicin-induced tumor membrane-coated iron (II)-cytosine-phosphate-guanine nanoparticles (DM@NPs) are shown for efficient co-delivery of tumor-associated antigens and adjuvant. Higher expression of ICD-related membrane proteins on the surface of the DM@NPs leads to the enhanced uptake of DM@NPs by dendritic cells (DCs), thereby promoting the DCs maturation and pro-inflammatory cytokines release. DM@NPs can remarkably increase the T cell infiltrations, remodel the tumor immune microenvironment and inhibit tumor progression in vivo. These findings reveal that pre-induced ICD tumor cell membrane-encapsulated nanoparticles can enhance immunotherapy responses and provide an effective biomimetic nanomaterial-based therapeutic strategy for lung cancer.

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