PDF(Pubmed)
Abstract：
Chemotherapy, as one main strategy to relieve tumor progression, has a weak effect on triple-negative breast cancer (TNBC) chest wall metastasis. The development of near-infrared (NIR) light-responsive nanomaterials for chemodynamic therapy (CDT) and photothermal therapy (PTT) is a promising platform but still challenging in biomedicine. This study reports a peroxidase mimicking nanozyme (Fe-N-C SAzyme) against TNBC by CDT and PTT. Fe-N-C SAzyme generated reactive oxygen species (ROS) by decomposing H2O2 into hydroxyl radicals (•OH) and also induced light-to-heat conversion under the exposure of 808 nm laser irradiation. With these biological characteristics, the obtained Fe-N-C SAzymes displayed enhanced cell cytotoxicity and inhibition of cancer cell proliferation both in vitro and in vivo at a low dose of nanoagent and a moderate NIR laser power density. Besides, Fe-N-C nanoagent with its excellent ROS generation brought metabolic reprogramming of elevated glycolysis in tumor cells. In vivo experiments, when combined with PTT, the enhanced antitumor effect was found by the elimination of M-MDSC in tumor microenvironment. Fe-N-C SAzymes can serve as a new synergistic CDT and PTT nanoagent to simultaneously reprogram tumor metabolism and tumor microenvironment. It will provide prospects for chemodynamic/photothermal combined cancer therapy for TNBC chest wall metastasis based on the use of a single nanosystem.
摘要：
化疗,作为缓解肿瘤进展的主要策略之一，对三阴性乳腺癌（TNBC）胸壁转移的影响较弱。用于化学动力疗法（CDT）和光热疗法（PTT）的近红外（NIR）光响应纳米材料的开发是一个有前途的平台，但在生物医学中仍然具有挑战性。这项研究报道了通过CDT和PTT针对TNBC的过氧化物酶模拟纳米酶（Fe-N-CSAzyme）。Fe-N-CSAzyme通过将H2O2分解为羟基自由基（•OH）而产生活性氧（ROS），并在808nm激光照射下诱导光热转化。有了这些生物学特性,在低剂量的纳米试剂和中等的NIR激光功率密度下，获得的Fe-N-CSAzymes在体外和体内均显示出增强的细胞毒性和对癌细胞增殖的抑制作用。此外,Fe-N-C纳米剂具有出色的ROS生成，可在肿瘤细胞中提高糖酵解的代谢重编程。体内实验,当与PTT结合使用时，通过消除肿瘤微环境中的M-MDSC发现了增强的抗肿瘤作用。Fe-N-C酶可以作为一种新的协同CDT和PTT纳米剂，同时重新编程肿瘤代谢和肿瘤微环境。基于单个纳米系统的使用，它将为TNBC胸壁转移的化学动力学/光热联合癌症治疗提供前景。
