AUTHOR=Ning Shipeng , Mo Jianlan , Huang Rong , Liu Benkun , Fu Bicheng , Ding Shuaijie , Yang Huawei , Cui Ying , Yao Lei 

TITLE=Injectable thermo-sensitive hydrogel loaded hollow copper sulfide nanoparticles for ROS burst in TME and effective tumor treatment

JOURNAL=Frontiers in Bioengineering and Biotechnology

VOLUME=11

YEAR=2023

URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2023.1191014

DOI=10.3389/fbioe.2023.1191014

ISSN=2296-4185

ABSTRACT=<p><bold>Introduction:</bold> Lung cancer the most prevalent cause of cancer-related deaths, and current therapies lack sufficient specificity and efficacy. This study developed an injectable thermosensitive hydrogel harboring hollow copper sulfide nanoparticles and β-lapachone (Lap) (CLH) for lung tumor treatment.</p><p><bold>Methods:</bold> The hydrogel-encapsulated CLH system can remotely control the release of copper ions (Cu<sup>2+</sup>) and drugs using photothermal effects for non-invasive controlled-release drug delivery in tumor therapy. The released Cu<sup>2+</sup> consumes the overexpressed GSH in TME and the generated Cu<sup>+</sup> further exploits the TME characteristics to initiate nanocatalytic reactions for generating highly toxic hydroxyl radicals. In addition, in cancer cells overexpressing Nicotinamide adenine dinucleotide (phosphate): quinone oxidoreductase 1 (NQO1), Lap can catalyze the generation of hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) through futile redox cycles. H<sub>2</sub>O<sub>2</sub> is further converted into highly toxic hydroxyl radicals via the Fenton-like reaction, leading to a burst of reactive oxygen species in TME, which further enhances the therapeutic effect of chemokines.</p><p><bold>Results:</bold> Analysis of the antitumor efficacy in a subcutaneous A549 lung tumor model mice showed a significant delay in tumor growth and no systemic toxicity was detected.</p><p><bold>Discussion:</bold> In conclusion, we have established a CLH nanodrug platform that enables efficient lung tumor therapy through combined photothermal/chemodynamic therapy (CDT) treatment and self-supplying H<sub>2</sub>O<sub>2</sub> to achieve cascade catalysis, leading to explosive amplification of oxidative stress.</p>