Cao Jie, Chen Dan, Huang Shanshan, Deng Dawei, Tang Liping, Gu Yueqing
Department of Biomedical Engineering, State Key Laboratory of Natural Medicines, School of Engineering, China Pharmaceutical University, Nanjing, China.
Department of Bioengineering, University of Texas at Arlington, Arlington, Texas, USA.
Oncotarget. 2016 Dec 13;7(50):82170-82184. doi: 10.18632/oncotarget.10320.
A combination of chemo- and photo-thermal therapy (PTT) has provided a promising efficient approach for cancer therapy. To achieve the superior synergistic chemotherapeutic effect with PTT, the development of a simple theranostic nanoplatform that can provide both cancer imaging and a spatial-temporal synchronism of both therapeutic approaches are highly desired. Our previous study has demonstrated that near-infrared (NIR) light-triggered biodegradable chitosan-based amphiphilic block copolymer micelles (SNSC) containing light-sensitive 2-nitrobenzyl alcohol and NIR dye cypate on the hydrophobic block could be used for fast light-triggered drug release. In this study, we conjugated the SNSC micelles with tumor targeting ligand c(RGDyK) and also encapsulated antitumor drug Paclitaxel (PTX). The results show that c(RGDyK)-modified micelles could enhance the targeting and residence time in tumor site, as well as be capable performing high temperature response for PTT on cancer cells and two-photon photolysis for fast release of anticancer drugs under NIR irradiation. In vitro release profiles show a significant controlled release effort that the release concentration of PTX from micelles was significantly increased with the exposure of NIR light. In vitro and in vivo antitumor studies demonstrate that, compared with chemo or PTT treatment alone, the combined treatment with the local exposure of NIR light exhibited significantly enhanced anti-tumor efficiency. These findings indicate that this system exhibited great potential in tumor-targeting imaging and synchronous chemo- and photo-thermal therapy.
化学疗法与光热疗法（PTT）相结合为癌症治疗提供了一种很有前景的有效方法。为了实现与PTT的卓越协同化疗效果，非常需要开发一种简单的诊疗纳米平台，该平台既能提供癌症成像，又能实现两种治疗方法的时空同步。我们之前的研究表明，基于近红外（NIR）光触发的可生物降解壳聚糖两亲性嵌段共聚物胶束（SNSC），其疏水嵌段上含有光敏性2-硝基苄醇和近红外染料cypate，可用于快速光触发药物释放。在本研究中，我们将SNSC胶束与肿瘤靶向配体c(RGDyK)偶联，并包封了抗肿瘤药物紫杉醇（PTX）。结果表明，c(RGDyK)修饰的胶束可以增强在肿瘤部位的靶向性和滞留时间，并且能够对癌细胞进行PTT的高温响应以及在近红外照射下进行双光子光解以实现抗癌药物的快速释放。体外释放曲线显示出显著的控释效果，即随着近红外光的照射，胶束中PTX的释放浓度显著增加。体外和体内抗肿瘤研究表明，与单独的化疗或PTT治疗相比，局部照射近红外光的联合治疗表现出显著增强的抗肿瘤效率。这些发现表明该系统在肿瘤靶向成像以及同步化疗和光热疗法方面具有巨大潜力。
