Aptamer-Modified Zinc Ferrite Nanoparticles for Autophagy-Mediated Chemotherapy and MR Imaging of Ovarian Cancer

Abstract

Chemotherapy resistance is a major cause of the high mortality in ovarian cancer. Therefore, there is an urgent need to develop strategies to increase the sensitivity of ovarian cancer to chemotherapeutic medicines. Here, we synthesized nucleic acid aptamer (NucA)-modified zinc ferrite nanoparticles (NAZs), to induce pro-death autophagy for enhancing the sensitivity of ovarian cancer cells to the chemotherapeutic agent�cisplatin (DDP). First, we verified that zinc ferrite nanoparticles (ZFONPs) effectively induced intact cellular autophagy in SKOV3 cells. Moreover, the use of small-molecule autophagy inhibitors markedly curtailed cell death induced by ZFONPs. Notably, we found that ZFONPs-induced pro-death autophagy was mediated by increasing zinc ion release and thereby intracellular reactive oxygen species (ROS) production. Second, we demonstrated that the modification of ZFONPs with the tumor-targeting aptamer (NucA) endowed the nanoparticles with the ability to target tumor cells. Furthermore, the induction of deathpromoting autophagy by NAZs sensitized ovarian cancer cells to DDP chemotherapy. Significantly, the constructed NAZs exhibited ovarian cancer targeting capabilities, served as T 2 -weighted magnetic resonance imaging (MRI) contrast agents, and enhanced the therapeutic effect of DDP in both in vitro and in vivo experiments. Collectively, these findings present a promising and effective approach for the precise treatment and diagnosis of ovarian cancer.