School of Materials Science and Engineering, Qingdao University of Science and Technology, Qingdao 266042, PR China.
Joint School of National University of Singapore and Tianjin University, International Campus of Tianjin University, Binhai New City, Fuzhou 350207, PR China.
ACS Nano. 2023 Aug 22;17(16):15605-15614. doi: 10.1021/acsnano.3c02370. Epub 2023 Jul 28.
Immunotherapy is an advanced therapeutic strategy of cancer treatment but suffers from the issues of off-target adverse effects, lack of real-time monitoring techniques, and unsustainable response. Herein, an ultrasmall Au nanocluster (NC)-based theranostic probe is designed for second near-infrared window (NIR-II) photoluminescence (PL) imaging-guided phototherapies and photoactivatable cancer immunotherapy. The probe (AuMBA-NLG for short) is composed of atomically precise and NIR-II emitting AuMBA NCs (here MBA denotes water-soluble 4-mercaptobenzoic acid) conjugated with immune checkpoint inhibitor 1-cyclohexyl-2-(5H-imidazo[5,1-]isoindol-5-yl)ethanol (NLG919) via a singlet oxygen (O)-cleavable linker. Upon NIR photoirradiation, the AuMBA-NLG not only enables NIR-II PL imaging of tumors in deep tissues for guiding tumor therapy but also allows the leverage of photothermal property for cancer photothermal therapy (PTT) and the photogenerated O for photodynamic therapy (PDT) and releasing NLG919 for cancer immunotherapy. Such a multiple effect modulated by AuMBA-NLG prompts the proliferation and activation of effector T cells, upshifts systemic antitumor T-lymphocyte (T cell) immunity, and finally suppresses the growth of both primary and distant tumors in living mice. Overall, this study may provide a promising theranostic nanoplatform toward NIR-II PL imaging-guided phototherapies and photoactivatable cancer immunotherapy.
免疫疗法是一种先进的癌症治疗策略，但存在脱靶不良反应、缺乏实时监测技术和反应不可持续等问题。在此，设计了一种基于超小 Au 纳米团簇（NC）的治疗诊断探针，用于近红外二区（NIR-II）光致发光（PL）成像引导的光疗和光活化癌症免疫治疗。该探针（AuMBA-NLG，简称）由原子精确且发射近红外二区光的 AuMBA NCs（这里 MBA 表示水溶性 4-巯基苯甲酸）与免疫检查点抑制剂 1-环己基-2-（5H-咪唑并[5,1-]异吲哚-5-基）乙醇（NLG919）通过单线态氧（O）可裂解的连接子连接而成。近红外光照射后，AuMBA-NLG 不仅能够对深层组织中的肿瘤进行 NIR-II PL 成像，以指导肿瘤治疗，还能够利用光热特性进行癌症光热治疗（PTT），以及光生成的 O 进行光动力治疗（PDT）和释放 NLG919 以进行癌症免疫治疗。这种由 AuMBA-NLG 调节的多种效应可促进效应 T 细胞的增殖和活化，上调系统抗肿瘤 T 淋巴细胞（T 细胞）免疫，最终抑制活体小鼠原发和远处肿瘤的生长。总体而言，该研究可能为近红外二区 PL 成像引导的光疗和光活化癌症免疫治疗提供一种有前途的治疗诊断纳米平台。
