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  3. 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

  • Mater Today Bio. 2025 Aug 16:34:102210. doi: 10.1016/j.mtbio.2025.102210.
Shipeng Dai 1,  Xunzheng Su 2,  Zhuozheng Li 3,  Hongyu Wang 1,  Li Liu 4 5,  Yuchen Xie 1,  Yue Chai 1,  Yueran Chen 6,  Zhaoyang Zhao 7,  Bo Luo 7,  Jie Kong 8,  Yanshu He 1,  Hengsong Cao 1,  Maiqi Xin 9,  Guoqiang Shao 6 7,  Yadong Shi 8,  Fei Xiong 2,  Weiwei Tang 1,  Jinhua Song 1
Affiliations

Affiliations

  • 1 Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing, China.
  • 2 State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering & Collaborative Innovation Center of Suzhou Nano-Science and Technology, Southeast University, Nanjing, China.
  • 3 School of Life Science and Technology, Shandong Second Medical University, Weifang, Shandong, China.
  • 4 First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.
  • 5 National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China.
  • 6 Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
  • 7 School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China.
  • 8 Department of Intervention, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
  • 9 Dingjiaqiao Campus, Nanjing Tech University, Nanjing, China.
PMID: 40893370 DOI: 10.1016/j.mtbio.2025.102210
Abstract

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.

Keywords

Hepatocellular carcinoma; Myeloid-derived suppressor cell; PD1; Phosphorus-32-loaded microspheres; Transarterial radioembolization.

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