Engineered Magnetic Resonance Nanoprobes for Visualizing Tumor Programmed Cell Death Ligand 1 Level and Enhancing Synergistic Radio Immunotherapy

Abstract

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 (Z_PD-L1) (GPPZ) was constructed. Leveraging the specific binding between Z_PD-L1 and the tumor surface, Z_PD-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, Z_PD-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.

Keywords: MRI; dimeric PD-L1 affibody; ferroptosis; nanoprobes; radio-immunotherapy.