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

Authors :
Yaoben Wang
Xiaobin Chen
Zhiyong Chen
Xin Wang
Hancheng Wang
Huajuan Zhai
Jiandong Ding
Lin Yu
Source :
Bioactive Materials, Vol 39, Iss , Pp 336-353 (2024)
Publication Year :
2024
Publisher :
KeAi Communications Co., Ltd., 2024.

Abstract

While mild hyperthermia holds great potential in the treatment of solid tumors, the thermal stress-triggered self-repairing autophagy significantly compromises its efficacy. To circumvent this obstacle, an injectable hydrogel (NO-Gel) composed of thermosensitive poly(ethylene glycol)-polypeptide copolymers modified with abundant NO 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 obtain MNPs@NO-Gel. The MNPs@NO-Gel system exhibits a sol-gel transition upon heating, and has the ability to perform multiple magnetic hyperthermia therapy (MHT) after only one administration due to the even distribution and strong immobilization of MNPs in NO-Gel. NO can be continuously liberated from NO-Gel and this process is markedly accelerated by MHT. Additionally, MNPs@NO-Gel maintains its integrity in vivo for over one month and the released MNPs are metabolized by the spleen. After a single administration of MNPs@NO-Gel at the tumor site, three mild MHT treatments with similar effects are fulfilled, and the sufficient supply of NO effectively inhibits MHT-induced autophagic flux via blocking the formation of autophagosomes and synchronously destroying lysosomes, thereby substantially boosting the efficacy of mild MHT. As a consequence, CT-26 colon tumors are completely eliminated without causing severe side-effects.

Details

Language :
English
ISSN :
2452199X
Volume :
39
Issue :
336-353
Database :
Directory of Open Access Journals
Journal :
Bioactive Materials
Publication Type :
Academic Journal
Accession number :
edsdoj.7b03dc1b52b14e38b358f74f08ce42fa
Document Type :
article
Full Text :
https://doi.org/10.1016/j.bioactmat.2024.05.032