pH and singlet oxygen dual-responsive GEM prodrug micelles for efficient combination therapy of chemotherapy and photodynamic therapy

Abstract

Nanocarriers have been an important strategy for enhancing the combination therapy of chemotherapy and photodynamic therapy (PDT) (Chem-PDT). However, conventional nanocarriers suffer from the problems of drug leakage in blood and insufficient drug release at target sites. Herein, we have designed a chlorin e6 (Ce6)-loaded GEM prodrug polymer micelle with a singlet oxygen cleavable linker and a pH responsive switch to avoid drug leakage in blood. These Ce6-loaded prodrug micelles possessed a uniform size distribution with a particle size of 78 nm. Meanwhile, the release of Ce6 and GEM was well controlled by acidic pH and laser irradiation. In addition, these micelles showed great acid triggered particle size shrinkage and charge-conversion properties, promoting micelle penetration at tumors and cellular uptake of micelles, which were confirmed by using CLSM of in vitro cell spheres and flow cytometry. Moreover, the in vitro and in vivo¹O₂ generation ability and antitumor ability of these micelles were impressive. This novel nanocarrier is a potential candidate for efficient Chem-PDT therapy.