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

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

Transarterial radioembolization (TARE) is a key therapy for hepatocellular carcinoma (HCC) management and downstaging. While 90Y microspheres (glass/resin) are widely used, their clinical application is limited by complexity, short half-life, and high costs. Thus, novel radionuclide microspheres are...

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Main Authors: Shipeng Dai, Xunzheng Su, Zhuozheng Li, Hongyu Wang, Li Liu, Yuchen Xie, Yue Chai, Yueran Chen, Zhaoyang Zhao, Bo Luo, Jie Kong, Yanshu He, Hengsong Cao, Maiqi Xin, Guoqiang Shao, Yadong Shi, Fei Xiong, Weiwei Tang, Jinhua Song
Format: Article
Language:English
Published: Elsevier 2025-10-01
Series:Materials Today Bio
Subjects:
Phosphorus-32-loaded microspheres
Hepatocellular carcinoma
Myeloid-derived suppressor cell
Transarterial radioembolization
PD1
Online Access:http://www.sciencedirect.com/science/article/pii/S259000642500780X
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Summary:Transarterial radioembolization (TARE) is a key therapy for hepatocellular carcinoma (HCC) management and downstaging. While 90Y 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 (32P-MS). In vitro, 32P-MS dose-dependently suppressed HCC cell proliferation, migration, and invasion while inducing apoptosis. In vivo, 32P-MS TARE achieved tumor vascular embolization, reducing tumor vol/wt (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 32P-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 32P-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 32P-MS with anti-PD1 therapy synergistically suppressed tumor growth, reduced MDSC infiltration, and reinvigorated CD8+ T cell activity, significantly improving treatment sensitivity. 32P-MS is a promising HCC therapeutic with dual anti-tumor and immune-modulatory functions, providing a compelling rationale for integrating radioembolization with immune checkpoint blockade to counteract immunosuppressive resistance in HCC.
ISSN:2590-0064

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