Cocktail strategy based on a dual function nanoparticle and immune activator for effective tumor suppressive

作者：Qian Li, Qiubing Chen, Xue Yang, Yuelan Zhang, Linyue Lv, Zhuyou Zhang, Shaowei Zeng, Jiaxi Lv, Sijin Liu, Bishi Fu · 发表于：Journal of Nanobiotechnology · 年份：2022 · DOI：10.1186/s12951-022-01241-y · 被引用次数：21 · 研究领域：interferon and immune responses、Nanoplatforms for cancer theranostics、Cancer Immunotherapy and Biomarkers

BACKGROUND: Immune checkpoint inhibitor-mediated immunotherapy cannot be carried out on a large scale clinically due to its low universality. In recent years, cyclic guanosine monophosphate synthase/interferon gene stimulating factor (cGAS/STING)-mediated innate immune signaling pathway-mediated immunotherapy has attracted more and more attention. In addition, metabolic inhibitors also show good effects on tumor treatment, but their application is often limited because of their large first pass effect or difficult administration. METHODS: The particle size and potential parameters were measured by DLS. In order to determine the optimal ratio of the two drugs, we calculated the CI value of different nanoparticles through MTT experiment, and simulated their synergistic effect through Gaussian software. Then the morphology and crystal form of the best proportion of drugs were studied by TEM and XRD. The anti-tumor mechanism of composite nanoparticles was confirmed by the determination of metabolic related indexes, Q-PCR and WB. The antitumor effect and immune activation effect were comprehensively evaluated by in vivo and in vitro experiments. RESULTS: Here, we found and synthesized BCP nanoparticles ((BPA + CPI) @ PLGA NPs) which can effectively reduce the metabolism of tumor cells and inhibit cell proliferation. At the same time, the release of mitochondrial DNA (mtDNA) caused by mitochondrial metabolism disorder further activated the cGAS/STING signal pathway in Hepa1-6 cells...