Highly stable photosensitive supramolecular micelles for tunable, efficient controlled drug release

作者： Belete Tewabe Gebeyehu^a; Ai-Wei Lee^b; Shan-You Huang^a; Adem Ali Muhabie^d; Juin-Yih Lai^a^,^c^,^f; Duu-Jong Lee^c^,^e; Chih-Chia Cheng^a

^aGraduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei 10607, Taiwan

^bDepartment of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan

^cDepartment of Chemical Engineering, National Taiwan University of Science and Technology, Taipei 10607, Taiwan

^dDepartment of Materials Science and Engineering, National Taiwan University of Science and Technology, Taipei 10607, Taiwan

^eDepartment of Chemical Engineering, National Taiwan University, Taipei 10617, Taiwan

^fR&D Center for Membrane Technology, Chung Yuan Christian University, Chungli, Taoyuan 32043, Taiwan

摘要：Simple fabrication and manipulation of multi-stimuli responsive supramolecular polymers based on multiple, self-complementary, hydrogen bond interactions with the desired self-assembly behavior and desirable micellar properties for effective drug delivery under physiological conditions remains a grand challenge. Herein, we successfully developed a dual light- and temperature-responsive uracil-based polymer, BU-PPG, that spontaneously self‐assembles to form micelle-shaped nanoparticles in phosphate-buffered saline (PBS) via supramolecular interactions between uracil moieties. The resulting micelles exhibited controlled light-sensitive photodimerization, a low critical micellization concentration, low cytotoxicity towards MCF-7 cells and tunable drug-loading capacity, as well as extremely high drug-entrapment stability in media containing serum. These features make BU-PPG micelles highly attractive as a potential candidate for safe, effective delivery of anticancer drugs. Importantly, when irradiated with UV light at 254?nm, the drug-loaded irradiated BU-PPG micelles could be easily tuned to obtain the desired phase transition temperature, remained highly stable under normal physiological conditions for prolonged periods of time, and rapidly released the encapsulated drug when the temperature was increased to 40?°C due to an efficient temperature-induced hydrophilic-hydrophobic phase transition. Collectively, these advantages suggest the newly developed BU-PPG supramolecular system may represent a promising new strategy towards the development of controlled release drug delivery systems.