Zhang Lingxiao, Jia Yingbo, Yang Jinju, Zhang Lun, Hou Shengjie, Niu Xiaoyun, Zhu Jie, Huang Yaru, Sun Xiaoying, Xu Zhi Ping, Liu Ruitian
State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.
Department of Pharmacology, School of Medicine, Zhejiang University City College, Hangzhou 310015, China.
ACS Nano. 2022 Aug 23;16(8):12036-12048. doi: 10.1021/acsnano.2c02183. Epub 2022 Jul 26.
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 . 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.
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，在该环境中，抗肿瘤免疫细胞受到抑制，肿瘤抗原持续突变或丢失。为了重塑TIME，我们在此应用弱碱性层状双氢氧化物纳米颗粒（LDH NPs）来中和过量的酸并阻断肿瘤细胞的自噬，以进行新辅助癌症免疫治疗。瘤周注射LDH NPs可在TIME中提供长期有效的酸中和作用，阻断肿瘤细胞中溶酶体介导的自噬途径，并提高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作为一种免疫调节剂和佐剂，成功地“唤醒”并促进了宿主的固有和适应性免疫系统，在实体瘤免疫治疗中显示出有前景的潜力。
