Engineering Au<sub>44</sub> Nanoclusters for NIR-II Luminescence Imaging-Guided Photoactivatable Cancer Immunotherapy
Yang Ge, Xinxin Pan, Wenbi Feng, Qiaofeng Yao, Fuyi Jiang, Fanglin Du, Xianfeng Zhou, Jianping Xie, Xun Yuan
Abstract
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 (Au 44 MBA 26 -NLG for short) is composed of atomically precise and NIR-II emitting Au 44 MBA 26 NCs (here MBA denotes water-soluble 4-mercaptobenzoic acid) conjugated with immune checkpoint inhibitor 1-cyclohexyl-2-(5H-imidazo[5,1- a ]isoindol-5-yl)ethanol (NLG919) via a singlet oxygen ( 1 O 2 )-cleavable linker. Upon NIR photoirradiation, the Au 44 MBA 26 -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 1 O 2 for photodynamic therapy (PDT) and releasing NLG919 for cancer immunotherapy. Such a multiple effect modulated by Au 44 MBA 26 -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.