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Tumor Microenvironment‐“AND” Near‐Infrared Light‐Activated Coordination Polymer Nanoprodrug for On‐Demand CO‐Sensitized Synergistic Cancer Therapy
Author(s) -
Sun Panpan,
Jia Le,
Hai Jun,
Lu Siyu,
Chen Fengjuan,
Liang Kun,
Sun Shihao,
Liu Hanwen,
Fu Xu,
Zhu Yanhong,
Wang Baodui
Publication year - 2021
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.202001728
Subject(s) - prodrug , glutathione , cancer therapy , chemistry , polymer , radical , in vivo , in vitro , cancer cell , tumor microenvironment , biophysics , combinatorial chemistry , cancer , biochemistry , cancer research , organic chemistry , tumor cells , enzyme , medicine , microbiology and biotechnology , biology
Carbon monoxide (CO) as an emerging treatment holds great promise for inducing the apoptosis of cancer cells. Here coordination assembled strategy is first reported for synthesis of Cu(II)‐flavone coordination polymer (NCu‐FleCP) CO nanoprodrug that is stable in normal physiological conditions, and yet readily reduces to small size prodrug complex and releases CO on demand under glutathione (GSH) and near infrared (NIR) light. Specifically, after uptaking by cancer cells, local GSH attacked coordination bond within NCu‐FleCP, resulting in the release of Cu(I) and free Fle. The CC bond of Fle is cleavage under NIR light to release CO for gas therapy, and Cu(I) reacts with local H 2 O 2 through Fenton like reaction to generate hydroxyl radicals ( • OH) for chemodynamic therapy. Detailed in vitro and in vivo experiments demonstrate that the CO prodrug system in generating a sufficient quantity of CO and • OH offers remarkable destructive effects against cancer cells without causing toxicity to surrounding normal tissues. The study provides a solid foundation to develop smart coordination polymer CO prodrugs with on‐demand CO release, enhanced permeability and retention effect, and biodegradability for multimodal synergistic therapy.