Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 6, Issue 13, Pages 10381-10392Publisher
AMER CHEMICAL SOC
DOI: 10.1021/am501913m
Keywords
cross-linking; photo sensitive; redox sensitive; micelle; drug delivery; dual responsive
Funding
- NIH/NCI [R01CA140449]
- Carol M. Baldwin Breast Cancer Research Foundation
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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 micro-environment 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.
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