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

Abstract

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 core–shell 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 core–shell UCNPs and DOX showed severe cell-killing effect under the assistance of a 980 nm diode laser. In vivo study in A549 tumor-bearing 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.

Light-Triggered Polymersome-Based Anticancer Therapeutics Delivery

“…Tsai et al developed photo- and redox-responsive polymersomes for cancer chemotherapy [ 293 ], where polymersomes were assembled by the double emulsion method from the synthetized amphiphilic diblock copolymer poly(ε-caprolactone)-ONB-SS-poly(methacrylic acid) (PCL-ONB-SS-PMAA). The two polymeric chains were linked through a responsive ONB ester next to a GSH-responsive disulfide linkage (SS).…”

Stimuli-Responsive Drug Delivery Systems for the Diagnosis and Therapy of Lung Cancer

“…To take advantage of both short-wavelength and NIR light, up-conversion nanoparticles (UCNPs), which are capable of transferring NIR light to short-wavelength light, are utilized to fulfill both deep penetration and short-wavelength light-responsive drug release. For example, Ming-Fong Tsai et al used a UV-responsive o-nitrobenzyl ester (ONB) containing amphiphilic block copolymer to construct a polymersome [ 26 ]. Then core-shell UCNPs and doxorubicin (DOX) were co-encapsulated to the polymersome, enabling NIR light-inducing photolysis and on-demand drug release for enhanced chemotherapy of lung cancer.…”

A multi-hit therapeutic nanoplatform for hepatocellular carcinoma: Dual stimuli-responsive drug release, dual-modal imaging, and in situ oxygen supply to enhance synergistic therapy

“…When these designed nanocarriers reached the acidic microenvironment (pH 5.0–6.5) of tumor cells, they could accelerate drug release from the nanocarriers [ [23] , [24] , [25] ]. The designed nanocarriers can also respond to external stimuli (e.g., temperature, light, and magnetic fields) to control the effective drug release at tumor sites, thereby avoiding in vivo toxicity caused by random drug release [ [26] , [27] , [28] , [29] ]. In addition, through ligand/biomarker/peptide modification, nanocarriers can actively target lesions to improve antitumor therapeutic effects [ [30] , [31] , [32] ].…”