Polymer prodrug-based nanoreactors activated by light for combined oxidation and chmotherapy

Abstract

We develop a prodrug-based nanoreactor system that can be specifically activated by light to in situ produce hydrogen peroxide (H2O2) and further trigger the release of free drugs for efficient cancer therapy. The block copolymers consist of hydrophilic poly (ethylene glycol (PEG) and hydrophobic copolymerized 2-(methacryloyloxy) ethyl camptothecin (CPT) oxalate (CPTMA) monomer and ROS-sensitive monomer. The copolymers are optimized to self-assemble into polymersomes (nanoreactors) in aqueous solution. Glucose oxidase (GOD) is encapsulated in hydrophilic cores. The photosensitizer is loaded in the hydrophobic membrane of polymersomes. Under near infrared (NIR) light irradiation, the photosensitizer generates ROS, which cleaves ROS-sensitive segments, increasing the membrane permeability of the polymersomes. Thus, glucose and oxygen (O2) can diffuse into the polyermsome core and lead to oxidation reaction under the catalysis of GOD. The produced H2O2 kills cancer cells and contributes to the release of active drug CPT from prodrug. The oxidation therapy by H2O2 and chemotherapy by CPT synergistically improve the antitumor efficacy. The morphology and size of polymersomes are characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The biocompatibility and antitumor efficacy of this system are evaluated in vitro and in vivo. The scientific results obtained from this project could advance the development of photo-responsive drug delivery systems for biomedical applications.