摘要
Glucose oxidase(GOx)-based nanotheranostic agents hold great promise in tumor starvation and its synergistic therapy. Self-assembled plasmonic gold vesicles(GVs) with unique optical properties, large hollow cavity, and strong localized surface plasmon resonance, can be used as multi-functional nanocarriers for synergistic therapy. Herein,GOx-loaded GVs(GV-GOx) were developed for light-triggered GOx release as well as enhanced catalytic activity of GOx, achieving programmable photothermal/starvation therapy. Under near-infrared laser irradiation, the GV-GOx generated strong localized hyperthermia due to plasmon coupling effect of GVs, promoting the release of encapsulated GOx and increasing its catalytic activity, resulting in enhanced tumor starvation effect. In addition, the high photothermal effect improved the cellular uptake of GV-GOx and allowed an efficient monitoring of synergistic tumor treatment via photoacoustic/photothermal duplex imaging in vivo. Impressively, the synergistic photothermal/starvation therapy demonstrated complete tumor eradication in 4 T1 tumorbearing mice, verifying superior synergistic anti-tumor therapeutic effects than monotherapy with no apparent systemic side effects. Our work demonstrated the development of a light-triggered nanoplatform for cancer synergistic therapy.
在肿瘤的饥饿治疗及协同治疗中,基于葡萄糖氧化酶(GOx)的纳米诊疗剂展现出具大的应用前景.自组装等离子体金囊泡(GV),由于具有独特的光学性能、巨大空腔和强局域表面等离子体共振等特性,可作为协同治疗的多功能纳米载体.本文中,我们开发了一种装载GOx的GV(GV-GOx)用于光触发释放GOx,同时增强GOx的催化活性,从而实现程序化光热-饥饿治疗.在近红外激光照射下,由于GV具有等离子体耦合效应, GV-GOx可以产生很强的局部高热,引起封装的GOx释放,同时高热可提高GOx催化活性,从而增强肿瘤的饥饿效应.此外,高光热效应可促进细胞对GV-GOx的摄取,并可通过活体光声/光热双模态成像对协同治疗进行有效监测.令人印象深刻的是,协同光热/饥饿疗法能完全消融4T1荷瘤小鼠的肿瘤,抗肿瘤效果明显优于单一疗法,且没有明显的系统毒性.本工作展示了一种光触发的纳米平台,可用于癌症协同治疗.
基金
supported by the National Natural Science Foundation of China (31771036 and 51703132)
the Basic Research Program of Shenzhen (JCYJ20180507182413022 and JCYJ20170412111100742)
Guangdong Province Natural Science Foundation of Major Basic Research and Cultivation Project(2018B030308003)
Fok Ying-Tong Education Foundation for Young Teachers in the Higher Education Institutions of China (161032)。
