Key Lab of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, College of Medicine, Yibin Institute of Southwest Jiaotong University, Southwest Jiaotong University, Chengdu, 610031, Sichuan, China.
Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu, 215123, China.
Biomaterials. 2022 Jan;280:121272. doi: 10.1016/j.biomaterials.2021.121272. Epub 2021 Nov 25.
Immunotherapy is a powerful way to treat cancer, however, systemic treatment-associated adverse effects remain a major concern. In this study, a bioadhesive injectable hydrogel is developed to provide localized immune niches for tumor microenvironment immunomodulation and cancer catalytic immunotherapy. First, a phenolic single atom nanozyme (SAN) was developed by in situ synthesis of Pd single atom on catechol-grafted carbon-quantum-dot (DA-CQD@Pd) templates. Then, the bioadhesive injectable hydrogel consisting of DA-CQD@Pd SAN and immune adjuvant CpGODN was formed through SAN-catalyzed free-radical polymerization. The SAN exhibited peroxidase-like activity to generate ROS and kill tumor cells through catalytic therapy. The hydrogel locally released CpGODN in a sustained manner, which limited the risk of systemic exposure, reducing the impact of CpGODN toxicity, and protecting CpGODN from degradation. The bioadhesive hydrogel immobilized around solid tumor to provide an immune response site after injection. When combined it with the administration of immune checkpoint inhibitor anti-PD-L1, the hydrogel realized localized immunomodulation, maximized therapeutic efficacy and prevents tumor metastasis via a catalytic immunotherapy.
免疫疗法是治疗癌症的一种有效方法，然而，全身治疗相关的不良反应仍然是一个主要关注点。在这项研究中，开发了一种生物粘附可注射水凝胶，以提供肿瘤微环境免疫调节和癌症催化免疫治疗的局部免疫龛。首先，通过在邻苯二酚接枝碳量子点（DA-CQD@Pd）模板上原位合成钯单原子，开发了一种酚类单原子纳米酶（SAN）。然后，通过 SAN 催化的自由基聚合形成由 DA-CQD@Pd SAN 和免疫佐剂 CpGODN 组成的生物粘附可注射水凝胶。SAN 表现出过氧化物酶样活性，通过催化治疗产生 ROS 并杀死肿瘤细胞。水凝胶以持续的方式局部释放 CpGODN，从而降低了全身暴露的风险，减轻了 CpGODN 毒性的影响，并保护 CpGODN 免受降解。生物粘附水凝胶固定在实体肿瘤周围，在注射后提供免疫反应部位。当与免疫检查点抑制剂抗 PD-L1 联合使用时，水凝胶通过催化免疫治疗实现局部免疫调节、最大化治疗效果并防止肿瘤转移。
