Near-Infrared Light-Triggered Drug Release from Ultraviolet- and Redox-Responsive Polymersome Encapsulated with Core-Shell Upconversion Nanoparticles for Cancer Therapy

Combining upconversion nanoparticles (UCNPs) and UV-sensitive polymers to form a smart drug delivery system (DDS) is a promising strategy to circumvent drawbacks of direct UV excitation in clinical applications. This study tuned up coreshell UCNPs with a shell thickness of 6 nm and emission wavelength falling in the ultraviolet region at 350 nm under near-infrared (NIR) light irradiation at 980 nm. An amphiphilic block copolymer with UV-responsive o-nitrobenzyl ester (ONB) next to a glutathione (GSH)-responsive disulfide linkage was synthesized and formulated into a polymersome. Core-shell UCNPs and doxorubicin (DOX) were simultaneously encapsulated into the polymersome during double emulsion for DDS. The combination of NIR light-inducing photolysis of the ONB linkage and GSH cleaving the disulfide linkage enhanced DOX release for chemotherapy. From in vitro evaluation, the polymersome alone was nontoxic against three lung cancer cell lines, but the one loaded with coreshell UCNPs and DOX showed severe cell-killing effect under the assistance of a 980 nm diode laser. In vivo study in A549 tumorbearing mice verified significant inhibition of tumor growth in mice treated with the polymersome containing core-shell UCNPs and DOX under 980 nm diode laser irradiation as compared with those without laser irradiation and those treated with free DOX. This intriguing nanomedicine of well-defined structures responsive to NIR light and reducing agents offers potential for smart DDS applications.

Automated summary

By tuning core-shell UCNPs with a shell thickness of 6 nm and utilizing NIR light-induced photolysis and GSH cleavage mechanisms, the study enhanced the release of doxorubicin, demonstrating potential for smart DDS applications.