Photosensitive Supramolecular Micelles with Complementary Hydrogen Bonding Motifs To Improve the Efficacy of Cancer Chemotherapy.

Photosensitive supramolecular micelles, a combination of intermolecular hydrogen bonds between complementary adenine (A) and uracil (U) groups and a blend of two types of supramolecular polymers, can stably self-assemble into structurally stable, spherical micelles in aqueous solution before and after photoirradiation. The resulting micelles possess unique amphiphilic properties, photo-induced tunable phase-transition behavior, excellent biocompatibility, well-controlled spherical morphology, and can be tailored in size. Moreover, the drug content and entrapment efficiency can be finely tuned, and release kinetics can be modulated using combinations of changes in temperature and photoirradiation, making these micelles highly addictive as drug nanocarriers. Importantly, cytotoxicity assays and flow cytometric analyses confirmed that drug-loaded irradiated micelles exerted more potent cytotoxic effects against cancer cells and exhibited much higher cellular uptake efficiency than the free drug and drug-loaded nonirradiated micelles, indicating that the drug-loaded irradiated micelles rapidly entered the tumor cells to induce massive cell death. Therefore, this newly-developed supramolecular system could serve as a safe, efficient nanocarrier to effectively inhibit the growth and spread of primary tumors.

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

HYPOTHESIS: Invoking 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. EXPERIMENTS: BU-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. FINDINGS: The 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.