State Key Laboratory of Luminescent Materials and Devices, College of Materials Science and Engineering, South China University of Technology (SCUT), Guangzhou, 510640, China.
State Key Laboratory of Luminescent Materials and Devices, College of Materials Science and Engineering, South China University of Technology (SCUT), Guangzhou, 510640, China.
Biomaterials. 2017 Sep;139:139-150. doi: 10.1016/j.biomaterials.2017.06.002. Epub 2017 Jun 7.
In vivo monitoring of the biodistribution and activation of prodrugs is highly attractive, and the self-immolative dendritic architecture is deemed as a promising approach for constructing theranostic prodrug in which the release/activation of different payloads is needed. Herein, A GSH-triggered and self-immolative dendritic platform comprising an anticancer drug camptothecin (CPT), a cleavable linker and a two-photon NIR fluorophore (dicyanomethylene-4H-pyran, DCM) has been developed for in situ tracking of drug release and antitumour therapy. In vitro experiments demonstrate that, the presence of glutathione (GSH) induces the cleavage of the self-immolative linker, resulting in comitant release of the drug and the dye. Upon cell internalization and under one- or two-photon excitation, prominent intracellular fluorescence can be observed, indicating the release of the payloads in live cells. Upon loaded in phospholipid vesicles, the prodrug has also been successfully utilized for in vivo and in situ tracking of drug release and cancer therapy in a mouse model. Several hours post injection, the prodrug generates strong fluorescence on tumour sites, demonstrating the prodrug's capability of monitoring the on-site drug release. Moreover, the prodrug shows considerable high activity and exerts obvious inhibition towards tumour growth. This work suggests that the prodrug with self-immolative dendritic structure can work well in vivo and this strategy may provide an alternative approach for designing theranostic drug delivery systems.
在体内监测前药的生物分布和激活非常有吸引力，自毁性树枝状架构被认为是构建治疗药物偶联体的有前途的方法，其中需要释放/激活不同的有效载荷。在此，设计了一种由抗癌药物喜树碱（CPT）、可切割连接子和双光子近红外荧光团（二氰基乙烯基-4H-吡喃，DCM）组成的 GSH 触发和自毁性树枝状平台，用于原位跟踪药物释放和抗肿瘤治疗。体外实验表明，谷胱甘肽（GSH）的存在会诱导自毁性连接子的断裂，从而导致药物和染料的共释放。在细胞内化后，在单光子或双光子激发下，可以观察到明显的细胞内荧光，表明在活细胞中释放了有效载荷。当负载在磷脂囊泡中时，前药还成功地用于在小鼠模型中进行体内和原位跟踪药物释放和癌症治疗。注射后数小时，前药在肿瘤部位产生强烈的荧光，表明前药具有监测现场药物释放的能力。此外，前药表现出相当高的活性，并对肿瘤生长表现出明显的抑制作用。这项工作表明，具有自毁性树枝状结构的前药在体内效果良好，这种策略可能为设计治疗药物传递系统提供一种替代方法。
