NIR-Activated Polymeric Nanoplatform with Upper Critical Solution Temperature for Image-Guided Synergistic Photothermal Therapy and Chemotherapy
NIR-Activated Polymeric Nanoplatform with Upper Critical Solution Temperature for Image-Guided Synergistic Photothermal Therapy and Chemotherapy
复制标题
用于图像引导协同光热疗法和化疗的具有上临界溶液温度的近红外激活聚合物纳米平台
DOI：
10.1021/acs.biomac.9b00321
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发表时间：
2019-06-01
影响因子：
6.2
通讯作者：
Zhang, Weian
中科院分区：
文献类型：
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作者：
Tian, Jia;Huang, Baoxuan;Zhang, Weian
药物过早和不完全释放是传统化疗药物释放的典型瓶颈。协同治疗可以弥补单一治疗的不足，显著提高治疗效果，在医学和生物学领域具有广泛的应用前景。本文构建了一种具有上临界溶液温度（UCST）的新型近红外（NIR）激活聚合物纳米平台，用于图像引导的协同光热治疗（PTT）和化疗。采用可逆加成-破碎链转移（RAFT）聚合法制备了ucst响应型两亲嵌段共聚物，并与IR780和卡巴他赛（Cab）共组装形成球形纳米粒子（NPs）。IR780/Cab双载UCST聚合物NPs在近红外激光照射下产生局部加热，进一步导致载货NPs解离和Cab的可控释放。IR780同时扮演加热发生器和“按需”药物释放激活剂的角色。体内荧光和光热成像的研究清楚地显示了肿瘤靶向性。值得注意的是，体外和体内研究都表明，PTT与化疗的协同作用比PTT与化疗的单独联合具有更好的抗癌效果。因此，定义良好的聚合物纳米平台为开发图像引导的肿瘤协同治疗开辟了一条多功能和有效的途径。
Premature and incomplete drug release is the typical bottleneck of drug release in traditional chemotherapy. Synergistic therapies are highly desirable in medicine and biology because they can compensate for the drawbacks of single therapy and significantly enhance the therapeutic efficacy. Herein, a novel near infrared (NIR)-activated polymeric nanoplatform with upper critical solution temperature (UCST) was constructed for image-guided synergistic photothermal therapy (PTT) and chemotherapy. UCST-responsive amphiphilic block copolymers were synthesized by reversible addition-fragmentation chain-transfer (RAFT) polymerization and then co-assembled with IR780 and cabazitaxel (Cab) to form spherical nanoparticles (NPs). IR780/Cab dual-loaded UCST polymeric NPs can produce local heating upon NIR laser irradiation and further lead to the dissociation of cargo-loaded NPs and controlled release of Cab. IR780 plays the role of both a heating generator and an activator for "on-demand" drug release. The investigation of in vivo fluorescence and photothermal imaging clearly demonstrated tumor targeting. Notably, both in vitro and in vivo studies illustrated that the synergistic PTT and chemotherapy presented better anticancer efficacy than that of PTT and chemotherapy simplely combined. Thus, the well-defined polymeric nanoplatform opens a versatile and effective path to develop image-guided synergistic therapies for tumor treatment.