Shao Yu, Shi Changying, Xu Gaofei, Guo DanDan, Luo Juntao
Department of Pharmacology, SUNY Upstate Cancer Research Institute, State University of New York Upstate Medical University , Syracuse, New York 13210, United States.
ACS Appl Mater Interfaces. 2014 Jul 9;6(13):10381-92. doi: 10.1021/am501913m. Epub 2014 Jun 25.
To develop a feasible and efficient nanocarrier for potential clinical application, a series of photo and redox dual responsive reversibly cross-linked micelles have been developed for the targeted anticancer drug delivery. The nanocarrier can be cross-linked efficiently via a clean, efficient, and controllable coumarin photodimerization within the nanocarrier, which simplify the formulation process and quality control prior clinical use and improve the in vivo stability for tumor targeting. At the same time, cross-linking of nanocarrier could be cleaved via the responsiveness of the built-in disulfide cross-linkage to the redox tumor microenvironment for on-demand drug release. Coumarin and disulfide bond was introduced into a linear-dendritic copolymer (named as telodendrimer) precisely via peptide chemistry. The engineered nanocarrier possesses good drug loading capacity and stability, and exhibits a safer profile as well as similar anticancer effects compared with free drug in cell culture. The in vivo and ex vivo small animal imaging revealed the preferred tumor accumulation and the prolonged tumor residency of the payload delivered by the cross-linked micelles compared to the non-cross-linked micelles and free drug surrogate because of the increased stability.
为开发一种适用于潜在临床应用的可行且高效的纳米载体，已研发出一系列光和氧化还原双响应的可逆交联胶束用于靶向抗癌药物递送。该纳米载体可通过纳米载体内清洁、高效且可控的香豆素光二聚作用实现高效交联，这简化了临床前使用的制剂工艺和质量控制，并提高了肿瘤靶向的体内稳定性。同时，纳米载体的交联可通过内置二硫键对氧化还原肿瘤微环境的响应而裂解，以实现按需药物释放。通过肽化学将香豆素和二硫键精确引入线性-树枝状共聚物（命名为端粒树枝状聚合物）。与游离药物相比，该工程化纳米载体具有良好的载药能力和稳定性，在细胞培养中表现出更安全的特性以及相似的抗癌效果。体内和体外小动物成像显示，与非交联胶束和游离药物替代物相比，由于稳定性增加，交联胶束递送的有效载荷在肿瘤中具有更好的蓄积和更长的停留时间。
