A multifunctional DNA repair enzyme and magnetic dual-triggered theranostic nanosystem for intelligent drug delivery

Abstract

Due to the high specificity and efficiency of enzymes, enzyme-responsive drug delivery systems are important in cancer therapy and diagnosis. Human apurinic/apyrimidinic endonuclease (APE1) is a representative DNA repair enzyme overexpressed in various cancer cells, which is also proven to be a promising stimuli in our previous studies. In this work, to realize targeted chemotherapy, an APE1 and magnetic dual-responsive nanocarrier was designed. The carrier is composed of Fe3O4@SiO2 nanoparticles and specially designed AP-DNA strand that can be effectively hydrolyzed by APE1. The chemotherapeutic drug doxorubicin (DOX) was loaded onto the AP-DNA to form the theranostic nanosystem (FS@DNA-DOX). As the AP-DNA was parted under the hydrolysis of APE1 in cancer cells, DOX was released to inhibit tumor growth. In vitro experiment results indicated that the nanosystem possesses a high specificity to APE1 and effectively release DOX in MCF-7 cells. In vivo experiments demonstrated that the targeted delivery of the nanosystem to the tumor site was successfully achieved and that strong tumor suppressor effects were observed. Overall, the FS@DNA-DOX is a multifunctional and theranostic nanosystem for the chemotherapy of cancer by increasing the therapeutic effect as well as reducing the toxicity of drugs.