Photothermally sensitive gold nanocage augments the antitumor efficiency of immune checkpoint blockade in immune “cold” tumors

Frontiers in Immunology

Immunology

Feng Luo¹  Chuan Zeng²  Xueyan Wang³  Jing Jing³  Yujie Zhao³  Guixiu Xiao⁴ 

[1] Department of Medical Oncology, Cancer Center, Lung Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China;Radiology Department, Sichuan Jianzhu Hospital, Chengdu, Sichuan, China;State Key Laboratory of Biotherapy, West China Hospital, Institute for Breast Health Medicine, Sichuan University, Chengdu, Sichuan, China;State Key Laboratory of Biotherapy, West China Hospital, Institute for Breast Health Medicine, Sichuan University, Chengdu, Sichuan, China;Department of Medical Oncology, Cancer Center, Lung Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China;

关键词: immune “cold” tumor;    immune checkpoint blockade;    immune microenvironment remodeling;    gold nanomaterials;    photothermal therapy;    melanoma;   

DOI  :  10.3389/fimmu.2023.1279221

 received in 2023-08-17, accepted in 2023-10-12,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionImmune checkpoint blockade (ICB) has revolutionized the therapy landscape of malignancy melanoma. However, the clinical benefits from this regimen remain limited, especially in tumors lacking infiltrated T cells (known as “cold” tumors). Nanoparticle-mediated photothermal therapy (PTT) has demonstrated improved outcomes in the ablation of solid tumors by inducing immunogenic cell death (ICD) and reshaping the tumor immune microenvironment. Therefore, the combination of PTT and ICB is a promising regimen for patients with “cold” tumors.MethodsA second near-infrared (NIR-II) light-activated gold nanocomposite AuNC@SiO2@HA with AuNC as a kernel, silica as shell, and hyaluronic acid (HA) polymer as a targeting molecule, was synthesized for PTT. The fabricated AuNC@SiO2@HA nanocomposites underwent various in vitro studies to characterize their physicochemical properties, light absorption spectra, photothermal conversion ability, cellular uptake ability, and bioactivities. The synergistic effect of AuNC@SiO2@HA-mediated PTT and anti-PD-1 immunotherapy was evaluated using a mouse model of immune “cold” melanoma. The tumor-infiltrating T cells were assessed by immunofluorescence staining and flow cytometry. Furthermore, the mechanism of AuNC@SiO2@HA-induced T-cell infiltration was investigated through immunochemistry staining of the ICD-related markers, including HSP70, CRT, and HMGB1. Finally, the safety of AuNC@SiO2@HA nanocomposites was evaluated in vivo.ResultsThe AuNC@SiO2@HA nanocomposite with absorption covering 1064 nm was successfully synthesized. The nano-system can be effectively delivered into tumor cells, transform the optical energy into thermal energy upon laser irradiation, and induce tumor cell apoptosis in vitro. In an in vivo mouse melanoma model, AuNC@SiO2@HA nanocomposites significantly induced ICD and T-cell infiltration. The combination of AuNC@SiO2@HA and anti-PD-1 antibody synergistically inhibited tumor growth via stimulating robust T lymphocyte immune responses.DiscussionThe combination of AuNC@SiO2@HA-mediated PTT and anti-PD-1 immunotherapy proposed a neoteric strategy for oncotherapy, which efficiently convert the immune “cold” tumors into “hot” ones.

【 授权许可】

Unknown   
Copyright © 2023 Xiao, Zhao, Wang, Zeng, Luo and Jing