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Ferrimagnetic m PEG-b-PHEP copolymer micelles loaded with iron oxide nanocubes and emodin for enhanced magnetic hyperthermia–chemotherapy

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National Science Review 2020年第4期7卷 723-736页

作者： Yonghong Song Dongdong Li Yang Lu Kun Jiang Yi Yang Yunjun Xu Liang Dong Xu Yan Daishun Ling Xianzhu Yang Shu-Hong Yu Key Laboratory of Advanced Catalytic Materials and Reaction Engineering School of Chemistry and Chemical EngineeringKey Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes Hefei University of Technology Institutes for Life Sciences School of Medicine South China University of Technology Division of Nanomaterials & Chemistry Hefei National Laboratory for Physical Sciences at the Microscale CAS Center for Excellence in Nanoscience Hefei Science Center of CASDepartment of Chemistry Institute of Biomimetic Materials & Chemistry University of Science and Technology of China Zhejiang Province Key Laboratory of Anti-Cancer Drug Research College of Pharmaceutical Sciences Key Laboratory of Biomedical Engineering of the Ministry of Education Zhejiang University

As a non-invasive therapeutic method without penetration-depth limitation, magnetic hyperthermia therapy(MHT) under alternating magnetic field(AMF) is a clinically promising thermal ***, the poor heating conversion efficiency and lack of stimulus–response obstruct the clinical application of magnetofluid-mediated MHT. Here, we develop a ferrimagnetic polyethylene glycol-poly(2-hexoxy-2-oxo-1,3,2-dioxaphospholane)(m PEG-b-PHEP) copolymer micelle loaded with hydrophobic iron oxide nanocubes and emodin(denoted as EMM). Besides an enhanced magnetic resonance(MR) contrast ability(r2= 271 m M-1s-1) due to the high magnetization, the specific absorption rate(2518 W/g at 35 k A/m) and intrinsic loss power(6.5 n Hm2/kg) of EMM are dozens of times higher than the clinically available iron oxide nanoagents(Feridex and Resovist), indicating the high heating conversion efficiency. Furthermore, this composite micelle with a flowable core exhibits a rapid response to magnetic hyperthermia, leading to an AMF-activated supersensitive drug release. With the high magnetic response, thermal sensitivity and magnetic targeting, this supersensitive ferrimagnetic nanocomposite realizes an above 70% tumor cell killing effect at an extremely low dosage(10 μg Fe/m L),and the tumors on mice are completely eliminated after the combined MHT–chemotherapy.

关键词： magnetic hyperthermia therapy sensitive thermal response chemotherapy magnetic targeting theranostics

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