首页|Self-fueling ferroptosis-inducing microreactors based on pH-responsive Lipiodol Pickering emulsions enable transarterial ferro-embolization therapy

Self-fueling ferroptosis-inducing microreactors based on pH-responsive Lipiodol Pickering emulsions enable transarterial ferro-embolization therapy

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Lipiodol chemotherapeutic emulsions remain one of the main choices for the treatment of unresectable hepatocellular carcinoma(HCC)via transarterial chemoembolization(TACE).However,the limited stability of Lipiodol chemotherapeutic emulsions would lead to rapid drug diffusion,which would reduce the therapeutic benefit and cause systemic toxicity of administrated chemotherapeutics.Therefore,the development of enhanced Lipiodol-based formulations is of great significance to enable effective and safe TACE treatment.Herein,a stable water-in-oil Lipiodol Pickering emulsion(LPE)stabilized by pH-dissociable calcium carbonate nanoparticles and hemin is prepared and utilized for efficient encapsulation of lipoxygenase(LOX).The obtained LOX-loaded CaCO3&hemin-stabilized LPE(LHCa-LPE)showing greatly improved emulsion stability could work as a pH-responsive and self-fueling microreactor to convert polyunsaturated fatty acids(PUFAs),a main component of Lipiodol,to cytotoxic lipid radicals through the cascading catalytic reaction driven by LOX and hemin,thus inducing ferroptosis of cancer cells.As a result,such LHCa-LPE upon transcatheter embolization can effectively suppress the progression of orthotopic N1S1 HCC in rats.This study highlights a concise strategy to prepare pH-responsive and stable LPE-based self-fueling microreactors,which could serve as bifunctional embolic and ferroptosis-inducing agents to enable proof-of-concept transarterial ferro-embolization therapy of HCC.

CaCO3 nanoparticlesPickering emulsionferroptosislipid peroxidationtransarterial ferro-embolization

Chunjie Wang、Lei Zhang、Zhijuan Yang、Dongxu Zhao、Zheng Deng、Jialu Xu、Yumin Wu、Yu Hao、Ziliang Dong、Liangzhu Feng、Zhuang Liu

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Institute of Functional Nano &Soft Materials(FUNSOM),Jiangsu Key Laboratory for Carbon-Based Functional Materials& Devices,Soochow University,Suzhou 215123,China

Center of Interventional Radiology & Vascular Surgery,Department of Radiology,Zhongda Hospital,Medical School,Southeast University,Nanjing 210009,China

Department of Interventional Radiology,The First Affiliated Hospital of Soochow University,Suzhou 215006,China

National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Research Programs from Ministry of Science and Technology(MOST)of ChinaNational Research Programs from Ministry of Science and Technology(MOST)of ChinaNatural Science Foundation of Jiangsu ProvinceCollaborative Innovation Center of Suzhou Nano Science and TechnologySuzhou Key Laboratory of Nanotechnology and BiomedicineHigher Education Discipline Innovation Project from the Ministry of Education of ChinaNew Cornerstone Science Foundation through the XPLORER PRIZE

5203200832322046220770932021YFF07018002022YFF0706500BK20220110

2024

10.1093/nsr/nwad257

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年,卷(期)：2024.11(1)
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