ACS nano · 2025
Engineered Magnetic Resonance Nanoprobes for Visualizing Tumor Programmed Cell Death Ligand 1 Level and Enhancing Synergistic Radio Immunotherapy.
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Sun Xiao, Gong Yufang, Ge Haiyan, Ma Guiqi, Yang Tianxing, Mu Mengyao, Zhang Le, Wang Chenyu, Shen Bowen, Dai Xiaohui, Wu Zhengyan, Zhang Xinyu, Fan Qing, Sun Hongzan
Аннотация
Visualizing tumor programmed cell death ligand 1 (PD-L1) expression and synchronously using this target for effective tumor therapy present great prospects for clinical application. In this study, a gadolinium-hybridized platinum nanoplatform with dimeric PD-L1-antagonistic affibody (ZPD-L1) (GPPZ) was constructed. Leveraging the specific binding between ZPD-L1 and the tumor surface, ZPD-L1 could endow this nanoplatform with efficient PD-L1 targeting, enabling the efficient magnetic resonance imaging (MRI) visualization of PD-L1 expression. GPPZ, through its catalase- and peroxidase-like activities, can catalyze the production of O2 and the production of •OH, respectively, sensitizing radiotherapy and enhancing immunogenic cell death. In addition, ZPD-L1 can also terminate T cells' immune suppression by effectively inhibiting interactions of PD-1/PD-L1 to further enhance tumor immunotherapy. Systemic delivery of GPPZ resulted in MRI contrast enhancement of tumors with high levels of PD-L1 expression. Importantly, no obvious side effects can be observed in both histological and hematology examination. Therefore, this nanoplatform demonstrated promise for enhanced MRI visualization of tumor PD-L1 level and synergistic radio immunotherapy.