Zhang Jingfang, Li Wenzhe, Qi Yafei, Wang Guorong, Li Lele, Jin Zhengyu, Tian Jie, Du Yang
Beijing Key Laboratory for Bioengineering and Sensing Technology, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, 100083, China.
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, China.
Angew Chem Int Ed Engl. 2023 Jan 26;62(5):e202214750. doi: 10.1002/anie.202214750. Epub 2022 Dec 27.
Immune checkpoint blockade has become a paradigm-shifting treatment modality to combat cancer, while conventional administration of immune checkpoint inhibitors, such as anti-PD-L1 antibody (α-PD-L1), often shows unsatisfactory immune responses and lead to severe immune-related adverse effects (irAEs). Herein, we develop a PD-L1 aptamer-based spherical nucleic acids (SNAs), which consists of oxaliplatin (OXA) encapsulated in a metal-organic framework nanoparticle core and a dense shell of aptPD-L1 (denoted as M@O-A). Upon light irradiation, this nanosystem enables concurrent photodynamic therapy (PDT), chemotherapy, and enhanced immunotherapy in one shot to inhibit both primary colorectal tumors and untreated distant tumors in mice. Notably, M@O-A shows scarcely any systemic immunotoxicity in a clinical irAEs-mimic transgenic mouse model. Collectively, this study presents a novel strategy for priming robust photo-immunotherapy against cancer with enhanced safety.
免疫检查点阻断已成为对抗癌症的一种范式转变的治疗方式，而传统的免疫检查点抑制剂给药方式，如抗PD-L1抗体（α-PD-L1），往往显示出不尽人意的免疫反应，并导致严重的免疫相关不良反应（irAEs）。在此，我们开发了一种基于PD-L1适配体的球形核酸（SNA），它由包裹在金属有机框架纳米颗粒核心中的奥沙利铂（OXA）和一层致密的aptPD-L1壳层组成（表示为M@O-A）。在光照射下，该纳米系统能够一次性同时实现光动力疗法（PDT）、化疗和增强免疫疗法，以抑制小鼠的原发性结直肠癌肿瘤和未治疗的远处肿瘤。值得注意的是，在临床irAEs模拟转基因小鼠模型中，M@O-A几乎没有任何全身免疫毒性。总的来说，这项研究提出了一种新的策略，用于启动针对癌症的强大光免疫疗法，并提高安全性。
