Targeted Chemo-Photodynamic Combination Platform Based on the DOX Prodrug Nanoparticles for Enhanced Cancer Therapy
Targeted Chemo-Photodynamic Combination Platform Based on the DOX Prodrug Nanoparticles for Enhanced Cancer Therapy
复制标题
基于 DOX 前药纳米颗粒的靶向化学光动力组合平台，用于增强癌症治疗
DOI：
10.1021/acsami.7b00927
复制
发表时间：
2017-04-19
影响因子：
9.5
通讯作者：
Liu, Jinjian
中科院分区：
文献类型：
--
作者：
Zhang, Yumin;Huang, Fan;Liu, Jinjian
化学光动力学联合治疗因其具有减少化疗药物毒副作用、提高治疗效果等优点，在肿瘤治疗中受到广泛关注。本研究分别通过巯基加成和席夫碱反应将RGD和DOX偶联到PEG上，制备了靶向和pH敏感的抗肿瘤前药纳米粒（RGD-PEG-DOX NPs，RGD-NPs）。随后，光敏剂二氢卟酚e6（Ce 6）被封装到RGD-NPs中，从而获得简单且高效的化学-光动力学组合平台（RGD-PEG-DOX/Ce 6 NPs，RGD-NPs/Ce 6）。该纳米颗粒具有化疗药物和光敏剂的高载药性能，并能在癌细胞的温和酸性微环境下同时释放，有望实现化疗和光动力治疗（PDT）的同步治疗。与游离的DOX和Ce 6相比，RGD-NPs/Ce 6可显著提高细胞对DOX和Ce 6的摄取能力，从而增加肿瘤细胞内ROS的含量，并对肿瘤细胞（MDA-MB-231细胞和MCF-7细胞）产生有效的细胞毒作用。体内实验表明，RGD-NPs/Ce 6显示出优于其他组（游离DOX、游离Ce 6和NPs/Ce 6）的肿瘤靶向、积累和保留能力，因此显著增强了激光辐射的体内抗肿瘤效果。病理学分析表明，纳米粒载药后，DOX引起的心脏毒性被彻底消除。因此，靶向化学-光动力学组合治疗平台可能是增强癌症治疗的有希望的候选者。
Chemo-photodynamic combination therapy has been received widespread attention in cancer treatment due to its excellent characteristics, such as reducing the adverse side effects of chemo-drugs and improving the therapeutic effects for various cancers. In this study, RGD and DOX was conjugated to PEG by thiol-ene addition and Schiff's base reaction, respectively, to prepare the targeted and pH-sensitive antitumor prodrug nanoparticles (RGD-PEG-DOX NPs, RGD-NPs). Subsequently, the photosensitizer chlorin e6 (Ce6) was encapsulated into RGD-NPs, thus obtaining a simple and efficient chemo-photodynamic combination platform (RGD-PEG-DOX/Ce6 NPs, RGD-NPs/Ce6). This nanoparticle possessed high drug loading property of both the chemo-drug and photosensitizer and could simultaneously release them under the mild acidic microenvironment of cancer cells, which was expected to realize the synchronization therapy of chemotherapy and photodynamic therapy (PDT). Compared with free DOX and Ce6, RGD-NPs/Ce6 could significantly improve the cellular uptake capacities of DOX and Ce6, resulting in the increased contents of ROS in cancer cells and effective cytotoxicity for tumor cells (MDA-MB-231 cells and MCF-7 cells) upon a laser radiation. The in vivo experiment showed that RGD-NPs/Ce6 displayed superior tumor targeting, accumulation, and retention ability than the other groups (free DOX, free Ce6 and NPs/Ce6), and thus significantly enhancing the antitumor effect in vivo with a laser radiation. In addition, the cardiotoxicity induced by DOX was thoroughly wiped out after being loaded and delivered by the nanoparticles according to the pathological analysis. Therefore, the targeted chemo-photodynamic combination therapeutic platform may be a promising candidate for enhanced cancer therapy.