College of Pharmaceutical Science, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, PR China.
MOE Key Laboratory of Mesoscopic Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, PR China.
Acta Biomater. 2019 Feb;85:218-228. doi: 10.1016/j.actbio.2018.12.020. Epub 2018 Dec 14.
In this study, an AIE-active polymer (FTP) was successfully prepared and employed to load anti-cancer drug doxorubicin (DOX) for self-indicating cancer therapy via dual FRET process. Our results demonstrated that the FTP polymer could self-assemble into nanoparticles (NPs) in aqueous solutions to give strong fluorescence emission via intramolecular FRET process. The DOX loaded FTP NPs (drug loading content: 21.77%) were homogeneous particles with size around 50 nm and neutral surface charge, which showed preferable colloidal stability, hemolysis and selective drug release with comparable in vivo antitumor effects to DOX·HCl. In particular, the FRET process between FTP (donor) and DOX (acceptor) could serve as indicator for monitoring the in vitro and in vivo drug release profile, which might be a promising platform to realize real-time monitoring of drug localization and release during the delivery process. STATEMENT OF SIGNIFICANCE: 1. An amphiphilic polymer containing aggregation-induced emission segments and polyethylene glycol (PEG) chains (FTP) was firstly synthesized, which is capable of exerting strong fluorescence via intramolecular Förster resonance energy transfer (FRET) in the aggregate state. 2. The FTP polymer could self-assembled into homogeneous nanoparticles in aqueous environment with decent DOX loading capacity. 3. The DOX loaded FTP nanoparticles can afford FRET-traceable monitoring of the drug release both in vitro and in vivo.
在这项研究中，成功制备了一种 AIE 活性聚合物（FTP），并通过双重 FRET 过程将其用于负载抗癌药物阿霉素（DOX）以进行自指示癌症治疗。我们的结果表明，FTP 聚合物可以在水溶液中自组装成纳米颗粒（NPs），通过分子内 FRET 过程产生强荧光发射。负载 DOX 的 FTP NPs（药物载药量：21.77%）是具有约 50nm 尺寸和中性表面电荷的均匀颗粒，具有良好的胶体稳定性、低溶血率和选择性药物释放，与 DOX·HCl 的体内抗肿瘤效果相当。特别地，FTP（供体）和 DOX（受体）之间的 FRET 过程可以作为监测体外和体内药物释放曲线的指示剂，这可能是实现药物定位和传递过程中释放的实时监测的有前途的平台。 意义声明：1. 首次合成了一种含有聚集诱导发射片段和聚乙二醇（PEG）链的两亲性聚合物（FTP），它在聚集态下通过分子内Förster 共振能量转移（FRET）能够发挥强烈的荧光。2. FTP 聚合物在水相环境中可以自组装成均匀的纳米颗粒，具有良好的 DOX 载药能力。3. 负载 DOX 的 FTP 纳米颗粒可以提供 FRET 可追踪的体外和体内药物释放监测。
