Light-responsive linear-dendritic amphiphilles and their nanomedicines for NIR-triggered drug release

Both ultraviolet (UV) and near-infrared (NIR) light-responsive linear-dendritic amphiphiles, PEO-D3DNQ, were click conjugated by connecting the diazonaphthoquinone (DNQ)-decorated poly(amido amine) dendron D3 (generation 3) and linear poly(ethylene oxide) (PEO) with molecular weights of 2 or 5 kDa. They self-assembled into spherical micelles with a hydrophobic DNQ core stabilized by a hydrophilic PEO corona in aqueous solution. As characterized by time-resolved UV-vis spectroscopy, dynamic light scattering and TEM, these micelles showed both UV- and NIR-sensitivity in phosphate buffer solution. Under 365 nm UV irradiation, the characteristic absorption intensity of DNQ progressively decreased and then leveled off within 8 minutes, suggesting the completion of the Wolff rearrangement of DNQ, while it took a longer time of 40-60 minutes to complete the Wolff rearrangement of DNQ under 808 nm NIR irradiation. Most of the micelles were disrupted after 30 minutes of BOB nm irradiation, and the apparent drug-release rate of the doxorubicin (DOX)-loaded micelles showed a nearly 8-fold increase, presenting a NIR-triggered drug-release profile. The DOX-loaded micelles could quickly enter into HeLa cells, release DOX inside the cells, and then kill the cells in a NIR-triggered manner, as evidenced by flow cytometry, confocal laser scanning microscopy, and MTT assay.