Phosphorus-32 microspheres: A dual-modality transarterial radioembolization approach for hepatocellular carcinoma therapy and Anti-PD1 immunotherapy potentiation

作者：Shipeng Dai, Xin Su, Z Li, Hongyu Wang, Li Liu, Yi Xie, Yue Chai, Yue Chen, Zhaoyang Zhao, Bo Luo, Jie Kong, Yanling He, Hengsong Cao, Maiqi Xin, Guoqiang Shao, Yadong Shi, Fei Xiong, Weiwei Tang, Jinhua Song · 发表于：Materials Today Bio · 年份：2025 · DOI：10.1016/j.mtbio.2025.102210 · 被引用次数：6 · 研究领域：Hepatocellular Carcinoma Treatment and Prognosis、Nanoplatforms for cancer theranostics、Nanoparticle-Based Drug Delivery

: Transarterial radioembolization (TARE) is a key therapy for hepatocellular carcinoma (HCC) management and downstaging. While 90 Y microspheres (glass/resin) are widely used, their clinical application is limited by complexity, short half-life, and high costs. Thus, novel radionuclide microspheres are crucial. This study developed phosphorus-32-loaded microspheres ( 32 P-MS). In vitro, 32 P-MS dose-dependently suppressed HCC cell proliferation, migration, and invasion while inducing apoptosis. In vivo, 32 P-MS TARE achieved tumor vascular embolization, reducing tumor volume/weight (confirmed by Positron Emission Tomography-Computed Tomography (PET-CT), Hematoxylin and Eosin (HE) staining, TUNEL/Ki67 assays without systemic toxicity. RNA sequencing and mass cytometry analyses revealed 32 P-MS upregulated FABP1 + PD-L1 + myeloid-derived suppressor cell (MDSC), linked to immunosuppression. Mechanistic investigations, including molecular docking, co-localization, and co-immunoprecipitation (Co-IP) assays, demonstrated that 32 P-MS activated the FABP1/PPARG/PD-L1 axis in MDSC. Genetic ablation of FABP1 or pharmacological inhibition with Orlistat reversed PD-L1 expression and augmented anti-tumor efficacy. Combining 32 P-MS with anti-PD1 therapy synergistically suppressed tumor growth, reduced MDSC infiltration, and reinvigorated CD8 + T cell activity, significantly improving treatment sensitivity. 32 P-MS is a promising HCC therapeutic with dual anti-tumor and immune-modulatory f...