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ACS Nano · 2022 · IF 18.027

Efficient Immunotherapy of Drug-Free Layered Double Hydroxide Nanoparticles via Neutralizing Excess Acid and Blocking Tumor Cell Autophagy

Lingxiao Zhang,Yingbo Jia,Jinju Yang,Lun Zhang,Shengjie Hou,Xiaoyun Niu,Jie Zhu,Yaru Huang,Xiaoying Sun,Zhi Ping Xu,Ruitian Liu

Cancer immunotherapy efficacy is largely limited by the suppressive tumor immune microenvironment (TIME) where antitumor immune cells are inhibited and tumor antigens continue to mutate or be lost. To remodel the TIME, we here applied weakly alkaline layered double hydroxide nanoparticles (LDH NPs) to neutralize the excess acid and block autophagy of tumor cells for neoadjuvant cancer immunotherapy. Peritumoral injection of LDH NPs provided a long-term and efficient acid-neutralization in the TIME, blocked the lysosome-mediated autophagy pathway in tumor cells, and increased the levels of antitumor tumor-associated macrophages and T cells. These LDH NPs captured tumor antigens released in the tumor tissues and effectively inhibited the growth of both melanoma and colon tumors in vivo. These findings indicate that LDH NPs, as an immunomodulator and adjuvant, successfully “awaken” and promote the host innate and adaptive immune systems, showing promising potential for solid tumor immunotherapy.

研究领域: 癌症研究 · 纳米技术 · 免疫学 · 生物医学工程
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