Entrapment of an adenine derivative by a photo-irradiated uracil-functionalized micelle confers controlled self-assembly behavior

Abstract

HypothesisInvoking cooperative assembly of the uracil-functionalized supramolecular polymer BU-PPG [uracil end-capped poly(propylene glycol)] upon association with the nucleobase adenine derivative A-MA [methyl 3-(6-amino-9H-purin-9-yl)propanoate] as a model drug provides a new concept to control and tune the properties of supramolecular complexes and holds significant potential for the development of safer, more effective drug delivery systems. ExperimentsBU-PPG and A-MA were successfully developed and exhibited specific recognition and high affinity, which enabled reversible complementary adenine-uracil (A-U) hydrogen bonding-induced formation of spherical micelles in aqueous solution. The self-assembly and controllable A-MA release behavior of BU-PPG/A-MA micelles were studied using morphological analysis and optical and light scattering techniques to investigate the effect of photoirradiation and temperature on the complementary hydrogen bond interactions between BU-PPG and A-MA. FindingsThe resulting micelles possess unusual physical properties, including controlled photoreactivity kinetics, controllable self-assembled morphology and low cytotoxicity in vitro, as well as reversible temperature-responsive behavior. Importantly, irradiated micelles exhibited excellent long-term structural stability under normal physiological conditions and serum disturbance. Increasing the temperature triggered rapid release of A-MA by disrupting A-U complexes. These findings represent an entirely new, promising strategy for the development of multi-controlled release drug delivery nanocarriers based on complementary hydrogen bonding interactions.