Autophagy inhibition mediated via an injectable and NO-releasing hydrogelfor amplifying the antitumor efficacy of mild magnetic hyperthermia  

作　　者：Yaoben Wang Xiaobin Chen Zhiyong Chen Xin Wang Hancheng Wang Huajuan Zhai Jiandong Ding Lin Yu 

机构地区：[1]State Key Laboratory of Molecular Engineering of Polymers,Department of Macromolecular Science,Shanghai Stomatological Hospital&School of Stomatology,Fudan University,Shanghai,200438,China

出　　处：《Bioactive Materials》2024年第9期336-353,共18页生物活性材料（英文）

基　　金：supported by the National Natural Science Foundation of China(grant no.21975045);Natural Science Foundation of Shanghai(grant no.23ZR1406800).

摘　　要：While mild hyperthermia holds great potential in the treatment of solid tumors, the thermal stress-triggered selfrepairingautophagy significantly compromises its efficacy. To circumvent this obstacle, an injectable hydrogel(NO-Gel) composed of thermosensitive poly(ethylene glycol)-polypeptide copolymers modified with abundantNO donors on their side chains is developed. Meanwhile, ferrimagnetic Zn0.5Fe2.5O4 magnetic nanoparticles(MNPs) with high magnetic-heat conversion efficiency are synthesized and loaded into NO-Gel to obtainMNPs@NO-Gel. The MNPs@NO-Gel system exhibits a sol-gel transition upon heating, and has the ability toperform multiple magnetic hyperthermia therapy (MHT) after only one administration due to the even distributionand strong immobilization of MNPs in NO-Gel. NO can be continuously liberated from NO-Gel and thisprocess is markedly accelerated by MHT. Additionally, MNPs@NO-Gel maintains its integrity in vivo for over onemonth and the released MNPs are metabolized by the spleen. After a single administration of MNPs@NO-Gel atthe tumor site, three mild MHT treatments with similar effects are fulfilled, and the sufficient supply of NOeffectively inhibits MHT-induced autophagic flux via blocking the formation of autophagosomes and synchronouslydestroying lysosomes, thereby substantially boosting the efficacy of mild MHT. As a consequence, CT-26colon tumors are completely eliminated without causing severe side-effects.

关 键 词：Mild hyperthermia Magnetic hyperthermia therapy(MHT) Autophagy inhibition Nitric oxide(NO) Injectable hydrogel 

分 类 号：TQ427.26[化学工程]