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

Abstract

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.