Selectively down-regulated PD-L1 by albumin-phenformin nanoparticles mediated mitochondrial dysfunction to stimulate tumor-specific immunological response for enhanced mild-temperature photothermal efficacy

光热治疗 癌症研究 免疫原性细胞死亡 转移 免疫疗法 化学 吲哚青绿 微泡 免疫系统 医学
作者
Zaigang Zhou,Ning Jiang,Jiashe Chen,Chunjuan Zheng,Yuanyuan Guo,Ruirong Ye,Ruogu Qi,Jianliang Shen
出处
期刊:Journal of Nanobiotechnology [Springer Nature]
卷期号:19 (1)
标识
DOI:10.1186/s12951-021-01124-8
摘要

Abstract Background Mild-temperature photothermal therapy (mild-PTT) has emerged as a highly promising antitumor strategy by triggering immunogenic cell death (ICD) to elicit both innate and adaptive immune responses for tumor control. However, mild-PTT still leads to the risk of tumor recurrence or metastasis because it could hardly completely eradicate tumors due to its impaired immunological efficacy owing to the enhanced PD-L1 expression in tumor cells after treatment. Results In this study, we described a hydrogen peroxide (H 2 O 2 ) responsive manganese dioxide mineralized albumin nanocomposite loading with mitochondria function inhibitor phenformin (PM) and near-infrared photothermal dye indocyanine green (ICG) by modified two-step biomineralization method. In combination with ICG induced mild-PTT and PM mediated mitochondria dysfunction, PD-L1 expression was obviously down-regulated and the generated immunological responses was able to effectively attack the remaining tumor cells. Meanwhile, the risk of tumor metastasis was effectively inhibited by reducing the expression of tumor invasion-related signal molecules (TGF-β and vimentin) after combining treatment. Conclusion Such a strategy offers novel insight into the development of nanomedicine for mild-PTT as well as cancer immunotherapy, which can provide protection against tumor relapse post elimination of their initial and metastatic tumors. Graphical Abstract
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