Ning Shipeng, Mo Jianlan, Huang Rong, Liu Benkun, Fu Bicheng, Ding Shuaijie, Yang Huawei, Cui Ying, Yao Lei
Guangxi Medical University Cancer Hospital, Nanning, China.
Department of Anesthesiology, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China.
Front Bioeng Biotechnol. 2023 May 2;11:1191014. doi: 10.3389/fbioe.2023.1191014. eCollection 2023.
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. The hydrogel-encapsulated CLH system can remotely control the release of copper ions (Cu) and drugs using photothermal effects for non-invasive controlled-release drug delivery in tumor therapy. The released Cu consumes the overexpressed GSH in TME and the generated Cu 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 (HO) through futile redox cycles. HO 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. 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. 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 HO to achieve cascade catalysis, leading to explosive amplification of oxidative stress.
肺癌是癌症相关死亡的最常见原因，而目前的治疗方法缺乏足够的特异性和疗效。本研究开发了一种含有中空硫化铜纳米颗粒和β-拉帕醌（Lap）的可注射热敏水凝胶（CLH）用于肺癌治疗。水凝胶包裹的CLH系统可利用光热效应远程控制铜离子（Cu）和药物的释放，用于肿瘤治疗中的非侵入性控释给药。释放的Cu消耗肿瘤微环境（TME）中过表达的谷胱甘肽（GSH），生成的Cu进一步利用TME特性引发纳米催化反应以产生高毒性的羟基自由基。此外，在过表达烟酰胺腺嘌呤二核苷酸（磷酸）：醌氧化还原酶1（NQO1）的癌细胞中，Lap可通过无效的氧化还原循环催化过氧化氢（HO）的生成。HO通过类芬顿反应进一步转化为高毒性的羟基自由基，导致TME中活性氧的爆发，进一步增强趋化因子的治疗效果。对皮下A549肺癌肿瘤模型小鼠的抗肿瘤疗效分析表明肿瘤生长显著延迟，且未检测到全身毒性。总之，我们建立了一个CLH纳米药物平台，通过联合光热/化学动力学疗法（CDT）治疗和自供应HO实现级联催化，从而导致氧化应激的爆发性放大，实现高效的肺癌治疗。
