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

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Efficient Immunotherapy of Drug-Free Layered Double Hydroxide Nanoparticles via Neutralizing Excess Acid and Blocking Tumor Cell Autophagy
ACS Nano ( IF 15.8 ) Pub Date : 2022-07-26 , DOI: 10.1021/acsnano.2c02183
Lingxiao Zhang _{1,

2,

3,

4} , Yingbo Jia _{1,

5} , Jinju Yang ₁ , Lun Zhang ₁ , Shengjie Hou _{1,

5} , Xiaoyun Niu ₁ , Jie Zhu ₁ , Yaru Huang _{1,

5} , Xiaoying Sun _{1,

5} , Zhi Ping Xu ₃ , Ruitian Liu ₁

Affiliation

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.

中文翻译：

通过中和过量酸和阻断肿瘤细胞自噬对无药物层状双氢氧化物纳米颗粒进行有效免疫治疗

癌症免疫疗法的疗效在很大程度上受到抑制性肿瘤免疫微环境 (TIME) 的限制，在该微环境中，抗肿瘤免疫细胞受到抑制，肿瘤抗原继续发生突变或丢失。为了改造 TIME，我们在这里应用弱碱性层状双氢氧化物纳米粒子 (LDH NPs) 来中和过量的酸并阻断肿瘤细胞的自噬，用于新辅助癌症免疫治疗。瘤周注射 LDH NPs 在 TIME 中提供了长期有效的酸中和作用，阻断了肿瘤细胞中溶酶体介导的自噬途径，并增加了抗肿瘤肿瘤相关巨噬细胞和 T 细胞的水平。这些 LDH NPs 捕获肿瘤组织中释放的肿瘤抗原，并在体内有效抑制黑色素瘤和结肠肿瘤的生长. 这些发现表明，LDH NPs 作为免疫调节剂和佐剂，成功“唤醒”并促进宿主先天性和适应性免疫系统，显示出实体瘤免疫治疗的巨大潜力。

更新日期：2022-07-26

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