pH-regulating Lipiodol Pickering emulsions enhance transarterial embolization therapy via inducing ferroptosis and activating antitumor immunity

  • Cell Rep Med. 2026 Mar 17;7(3):102662. doi: 10.1016/j.xcrm.2026.102662.
Weihao Yang  1 ,  Chunjie Wang  2 ,  Chao Yu  3 ,  Nan Jiang  1 ,  Bin Yu  1 ,  Yicheng Ni  3 ,  Caifang Ni  4 ,  Liangzhu Feng  5 ,  Lei Zhang  6
Affiliations
  • 1. Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
  • 2. Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, China.
  • 3. Center of Interventional Radiology and Vascular Surgery, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Department of Radiology, Zhongda Hospital, Medical School, Southeast University, No. 87 Dingjiaqiao Road, Nanjing 210009, China.
  • 4. Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China. Electronic address: [email protected].
  • 5. Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, China. Electronic address: [email protected].
  • 6. Center of Interventional Radiology and Vascular Surgery, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Department of Radiology, Zhongda Hospital, Medical School, Southeast University, No. 87 Dingjiaqiao Road, Nanjing 210009, China. Electronic address: [email protected].
PMID: 41850231 DOI: 10.1016/j.xcrm.2026.102662
Abstract

Transcatheter arterial chemoembolization (TACE) faces limitations in hepatocellular carcinoma (HCC) due to suboptimal drug pharmacokinetics and immunosuppression post-embolization. This study develops iron nanoparticles (FeNPs) with pH-responsive Fenton activity as Surfactants for a Lipiodol Pickering emulsion (LPE) to deliver cariporide, targeting tumor acidity. Cariporide inhibits plasma membrane sodium-hydrogen exchangers, reducing intracellular pH to amplify FeNP-induced Ferroptosis while suppressing extracellular acidosis by blocking proton extrusion. The cariporide-loaded FeNP-LPE (CFe-LPE) promotes immunogenic cell death and reverses immunosuppressive tumor microenvironments by alleviating acidity. In multiple orthotopic HCC models, CFe-LPE-based transarterial embolization outperforms conventional doxorubicin-Lipiodol TACE, demonstrating that dual modulation of intra/extracellular pH enhances Fenton-catalytic embolic agents by synergistically activating antitumor immunity.

Keywords
Lipiodol Pickering emulsion; ferroptosis; transarterial embolization; tumor acidity regulation; tumor immunosuppression.
Products