CAS Key Laboratory of Chemistry of Northwestern Plant Resources and Key Laboratory for Natural Medicine of Gansu Province, Lanzhou Institute of Chemical Physics , Chinese Academy of Sciences (CAS) , Lanzhou 730000 , P. R. China.
ACS Appl Mater Interfaces. 2018 Jun 27;10(25):21149-21159. doi: 10.1021/acsami.8b05170. Epub 2018 Jun 18.
The development of codelivery systems for combination therapy that can load different drugs in a single carrier and precisely deliver payloads (ratio and administration time) via programmable administration has proven to be challenging. By taking advantage of the increased dimension or space from particle self-assembly approach, we have developed a prodrug-based cascade self-assembly strategy to construct a supramolecular hydrogel that can load different drugs in stages yet temporally/spatially release drugs by cascade disassembly of supramolecular hydrogel under different microenvironments. The cascade self-assembly mechanism has been investigated in detail by morphology evolution of prodrug micelles. Using tumor cell uptake, cytotoxicity assay, and a tumor-bearing animal model, the effectiveness of the prodrug micelle-based cascade self-assembly system was studied, such as loading, controlling the drug ratio, and the administration time for possible therapeutic applications. These studies fully demonstrate the proof of concept and open up an attractive new way to construct multidrug-loaded carriers for combination therapy.
载药系统的发展对于联合治疗具有重要意义，它可以将不同的药物装载在单一载体中，并通过可编程的给药方式精确地输送药物（比例和给药时间）。利用自组装颗粒增加维度或空间的优势，我们开发了一种基于前药的级联自组装策略，构建了一种超分子水凝胶，该水凝胶可以分阶段装载不同的药物，并通过在不同微环境下级联解超分子水凝胶来实现药物的时空释放。通过前药胶束的形态演变详细研究了级联自组装机制。通过肿瘤细胞摄取、细胞毒性测定和荷瘤动物模型研究了前药胶束为基础的级联自组装系统的有效性，例如装载、控制药物比例以及给药时间等，以满足可能的治疗应用。这些研究充分证明了该概念的可行性，并为构建用于联合治疗的多药物载体提供了一种有吸引力的新方法。
