Visible-light-sensitive titanium dioxide nanoplatform for tumor-responsive Fe2+ liberating and artemisinin delivery

// Huijuan Zhang 1, 2, 3 , Hongling Zhang 1, 2, 3 , Xing Zhu 1 , Xiaoge Zhang 1 , Qianqian Chen 1 , Jianjiao Chen 1 , Lin Hou 1, 2, 3 and Zhenzhong Zhang 1, 2, 3 1 School of Pharmaceutical Sciences, Zhengzhou University, Henan Province, Zhengzhou, China 2 Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Henan Province, Zhengzhou, China 3 Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Zhengzhou, China Correspondence to: Zhenzhong Zhang, email: zhangzz08@126.com Lin Hou, email: houlin_pharm@163.com Keywords: Fe 2+ -dependent drug, visible-light-sensitive ROS production, tumor-responsive Fe 2+ liberating Received: October 06, 2016      Accepted: April 16, 2017      Published: May 05, 2017 ABSTRACT Artemisinin is a kind of Fe 2+ -dependent drugs. Artemisinin and Fe 2+ co-transport systems can improve its anti-tumor effect. In this study, a visible light-sensitive nanoplatform (HA-TiO 2 -IONPs/ART) was developed. Detailed investigation demonstrated that HA-TiO 2 -IONPs/ART could realize Fe 2+ and artemisinin synchronous co-delivery and tumor-responsive release. This feature enhanced the anti-tumor efficiency of artemisinin significantly. In vitro results proved that hyaluronic acid modification could improve the biocompatibility, dispersion stability and cytophagy ability of nanocarriers. Furthermore, this drug delivery system could generate reactive oxygen species under visual light irradiation. In vitro and in vivo experiments demonstrated that HA-TiO 2 -IONPs/ART combining with laser irradiation displayed the best anti-tumor efficacy. This study affords a promising idea to improve the curative efficiency of artemisinin analogs for cancer therapy.