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

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

机构地区：[1]Institute of Functional Nano&Soft Materials(FUNSOM),Jiangsu Key Laboratory for Carbon-Based Functional Materials&Devices,Soochow University,Suzhou 215123,China [2]Center of Interventional Radiology&Vascular Surgery,Department of Radiology,Zhongda Hospital,Medical School,Southeast University,Nanjing 210009,China [3]Department of Interventional Radiology,The First Affiliated Hospital of Soochow University,Suzhou 215006,China

出　　处：《National Science Review》2024年第1期69-80,共12页国家科学评论（英文版）

基　　金：partially supported by the National Natural Science Foundation of China (52032008, 32322046 and 22077093);the National Research Programs from Ministry of Science and Technology (MOST) of China (2021YFF0701800 and2022YFF0706500);the Natural Science Foundation of Jiangsu Province (BK20220110);the Collaborative Innovation Center of Suzhou Nano Science and Technology;the Suzhou Key Laboratory of Nanotechnology and Biomedicine;the Higher Education Discipline Innovation Project from the Ministry of Education of China;the New Cornerstone Science Foundation through the XPLORER PRIZE。

摘　　要：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 CaCO_(3)&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.

关 键 词：CaCO_(3) nanoparticles Pickering emulsion ferroptosis lipid peroxidation transarterial ferro-embolization 

分 类 号：R943[医药卫生—药剂学]