Radiation-activated PD-L1 aptamer-functionalized nanoradiosensitizer to potentiate antitumor immunity in combined radioimmunotherapy and photothermal therapy

• Published in: Journal of materials chemistry. B, Materials for biology and medicine Materials for biology and medicine, 2024-12, Vol.12 (47), p.1222-12231
• Main Authors: Chen, Bo, He, Yinbo, Bai, Long, Pan, Shulin, Wang, Yinggang, Mu, Min, Fan, Rangrang, Han, Bo, Huber, Peter Ernst, Zou, Bingwen, Guo, Gang
• Format: Article
• Language: English
• Subjects: Animals; Anticancer properties; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antitumor activity; Apoptosis; Aptamers; Aptamers, Nucleotide - chemistry; Aptamers, Nucleotide - pharmacology; B7-H1 Antigen - antagonists & inhibitors; B7-H1 Antigen - metabolism; Cell activation; Cell death; Cell Line, Tumor; Female; Gold - chemistry; Gold - pharmacology; Humans; Hypoxia; Immune checkpoint inhibitors; Immune Checkpoint Inhibitors - chemistry; Immune Checkpoint Inhibitors - pharmacology; Immune system; Immunity; Immunogenicity; Lymphocytes; Lymphocytes T; Macrophages; Manganese Compounds - chemistry; Manganese Compounds - pharmacology; Manganese dioxide; Mice; Mice, Inbred C57BL; Oxides - chemistry; Oxides - pharmacology; Particle Size; PD-L1 protein; Photothermal conversion; Photothermal Therapy; Radiation dosage; Radiation therapy; Radioimmunotherapy - methods; Reactive oxygen species; Reactive Oxygen Species - metabolism; Tumor microenvironment; Tumor Microenvironment - drug effects; Tumors
• ISSN: 2050-750X; 2050-7518; 2050-7518
• DOI: 10.1039/d4tb01831a

Reactive oxygen species (ROS)-mediated immunogenic cell death (ICD) is crucial in radioimmunotherapy by boosting innate antitumor immunity. However, the hypoxic tumor microenvironment (TME) often impedes ROS production, limiting the efficacy of radiotherapy. To tackle this challenge, a combination therapy involving radiotherapy and immune checkpoint blockade (ICB) with anti-programmed death-ligand 1 (PD-L1) has been explored to enhance antitumor effects and reprogram the immunosuppressive TME. Here, we introduce a novel PD-L1 aptamer-functionalized nanoradiosensitizer designed to augment radiotherapy by increasing X-ray deposition specifically at the tumor site. This innovative X-ray-activated nanoradiosensitizer, comprising gold-MnO 2 nanoflowers, efficiently enhances ROS generation under single low-dose radiation and repolarizes M2-like macrophages, thereby boosting antitumor immunity. Additionally, the ICB inhibitor BMS-202 synergizes with the PD-L1 aptamer-assisted nanoradiosensitizer to block the PD-L1 receptor, promoting T cell activation. Furthermore, this nanoradiosensitizer exhibits exceptional photothermal conversion efficiency, amplifying the ICD effect. The PD-L1-targeted nanoradiosensitizer effectively inhibits primary tumor growth and eliminates distant tumors, underscoring the potential of this strategy in optimizing both radioimmunotherapy and photothermal therapy. This gold-MnO 2 nanoradiosensitizer enhances radioimmunotherapy by boosting ROS production, triggering immunogenic cell death, and effectively suppressing tumor growth and metastasis.