NIR responsive nanoenzymes via photothermal ablation and hypoxia reversal to potentiate the STING-dependent innate antitumor immunity

Qianzhe Li; Mengyu Yang; Xin Sun; Qinxin Wang; Beibei Yu; Aihua Gong; Miaomiao Zhang; Fengyi Du

doi:10.1016/j.mtbio.2023.100566

NIR responsive nanoenzymes via photothermal ablation and hypoxia reversal to potentiate the STING-dependent innate antitumor immunity

Mater Today Bio. 2023 Jan 29:19:100566. doi: 10.1016/j.mtbio.2023.100566. eCollection 2023 Apr.

Authors

Qianzhe Li^{1

2}, Mengyu Yang², Xin Sun², Qinxin Wang², Beibei Yu², Aihua Gong², Miaomiao Zhang², Fengyi Du^{1

2}

Affiliations

¹ Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu University 212013, PR. China.
² Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, PR. China.

Abstract

Despite advances in combined photothermal/immunotherapy of tumor, the therapeutic effect has been impaired due to hypoxic microenvironment and inadequate immune activation. Manganese ions directly activated the stimulator of interferon genes (STING) pathway and induced innate antitumor immunity. Herein, a near infrared light (NIR)-responsive nanoenzyme (PB-Mn/OVA NE) was constructed by doping manganese into the ovalbumin (OVA)-templated Prussian blue (PB) nanoparticles. The resultant PB-Mn/OVA NEs exhibited favorable catalase activity to produce oxygen, which was conducive to alleviate the tumor hypoxic microenvironment. Under 808 nm NIR irradiation, the PB-Mn/OVA NEs with outstanding photothermal conversion efficiency of 30% significantly destroyed tumor cells by inducing immunogenic cell death (ICD). Impressively, the PB-Mn/OVA NEs could activate the cGAS-STING pathway to promote the maturation and the antigen cross-presentation ability of dendritic cells (DCs), which further activated cytotoxic T lymphocytes and memory T lymphocytes. Overall, this work presents a powerful nanoenzyme formula to integrate photothermal ablation and hypoxic reversal for triggering robust innate and adaptive antitumor immune response.

Keywords: Hypoxic reversal; Nanoenzyme; Photothermal therapy; Prussian blue; cGAS-STING.