Light-cross-linked small-molecule micelles with enediyne units are designed for developing efficient drug-delivery systems. Gemcitabine (GEM) is chosen as a model hydrophilic drug and tethered with a maleimide-based enediyne (EDY) as a hydrophobic tail in the preparation of amphiphilic EDY-GEM. The stable micellar particles are obtained by cross-linking the enediyne moieties via photoinduced Bergman cyclization polymerization in aqueous media. The light-cross-linked spherical micelles with a size of 80 nm are characterized with dynamic light scattering and electron microscopy, showing robust micellar stability, bright fluorescent emission due to their intrinsic conjugated structure, and potential passive tumor-targeting ability through the enhanced permeability and retention effect. The drug-loaded micelles, as an example of light-cross-linked small-molecule micelle-based drug-delivery system, exhibit high drug-loading contents (50%) and greatly improved cytotoxicity toward A549 cells (decreasing the IC50 value of Gemcitabine by 10 times), thanks to the greatly increased cellular uptake of the drug-loaded micelles as confirmed by confocal laser scanning microscopy. The light-cross-linked enediyne-based small-molecule micelles system therefore provides a simple yet efficient drug-delivery platform for cancer chemotherapy.
Keywords: cytotoxicity; drug delivery; enediynes; light-cross-linked; small-molecule micelles.