A new light-sensitive polymer containing multiple light-sensitive triggering groups along the backbone and incorporating a quinone-methide self-immolative moiety was developed and formulated into nanoparticles encapsulating a model dye Nile Red. Triggered burst-release of the payload upon irradiation and subsequent degradation of the nanoparticles was observed. This system is designed to be versatile where the triggering group can be sensitive to a number of wavelengths.

Near infrared (NIR) irradiation can penetrate up to 10 cm deep into tissues and be remotely applied with high spatial and temporal precision. Despite its potential for various medical and biological applications, there is a dearth of biomaterials that are responsive at this wavelength region. Herein we report a polymeric material that is able to disassemble in response to biologically benign levels of NIR irradiation upon two-photon absorption. The design relies on the photolysis of the multiple pendant 4-bromo7-hydroxycoumarin protecting groups to trigger a cascade of cyclization and rearrangement reactions leading to the degradation of the polymer backbone. The new material undergoes a 50% Mw loss after 25 sec of ultraviolet (UV) irradiation by single photon absorption and 21 min of NIR irradiation via two-photon absorption. Most importantly, even NIR irradiation at biologically benign laser power is sufficient to cause significant polymer disassembly. Furthermore, this material is well tolerated by cells both before and after degradation. These results demonstrate for the first time a NIR sensitive material with potential to be used for in vivo applications.