Enzyme and pH-responsive nanovehicles for intracellular drug release and photodynamic therapy

Abstract

Currently, functional nanocomposites consisting of multiple therapy properties have attracted significant attention in the development of anticancer therapeutic agents. Herein, an enzyme and pH-responsive nanocomposite was constructed for sensitive intracellular drug release and photodynamic therapy (PDT). The nanocarrier, about 75 nm in size, is composed of an upconversion nanoparticle (UCNP, NaYF₄:Yb,Er@NaYF₄) core and mesoporous silica shell doped with chlorine e6 (Ce6) (UCNP@mSiO₂-Ce6). Then, the sensitive linker succinic acid–glycine–phenylalanine–leucine–glycine (SGFLG) was prepared and grafted on to the nanovehicle to encapsulate the anticancer drug doxorubicin (DOX). The in vitro release kinetics was studied to reveal the sensitive DOX release, depending on the enzyme (cathepsin B) concentration and pH value. To further ensure the targeting of the tumor tissue, transferrin (Tf) was grafted, and then cellular uptake/release studies were carried out using HeLa as a model cancer cell and L02 (normal liver cell) as the control. The enhanced cytotoxicity towards HeLa over L02 cells is ascribed to the excess expression of Tf receptors, high concentration of cathepsin B, and the lower pH environment in cancer cells. In addition, under NIR irradiation, the visible light emission could excite Ce6 to generate reactive oxygen and to achieve PDT, which is associated with sensitive chemotherapy to further improve the specific cytotoxicity. The novel nanoplatform has potential application in cancer treatment.