Manganese dioxide nanosheets-based redox/pH-responsive drug delivery system for cancer theranostic application

Yongwei Hao,1,* Lei Wang,1,2,* Bingxiang Zhang,1 Dong Li,1 Dehui Meng,1 Jinjin Shi,1 Hongling Zhang,1 Zhenzhong Zhang,1 Yun Zhang11School of Pharmaceutical Sciences, 2School of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou, People’s Republic of China *These authors contributed equally to this work Abstract: The aim of this study was to construct redox- and pH-responsive degradable manganese dioxide (MnO2) nanosheets for cancer theranostic application. The small MnO2 nanosheets were synthesized, and then functionalized by hyaluronic acid (HA), demonstrating excellent stability and tumor-targeting ability. Cisplatin (cis-diamminedichloroplatinum [CDDP]) was absorbed by the nanosheets through a physical action, which was designed as MnO2/HA/CDDP. The prepared MnO2/HA/CDDP formulation was able to efficiently deliver CDDP to tumor cells in vitro and in vivo, resulting in improved therapeutic efficiency. Subsequently, they were triggered by lower pH and higher level of reduced glutathione to generate Mn2+, enabling magnetic resonance imaging. The smart multifunctional system combining efficient magnetic resonance imaging and chemotherapy has the potential to be used as a tumor-targeting theranostic nanomedicine.Keywords: manganese dioxide nanosheets, hyaluronic acid, magnetic resonance imaging, theranostic applicatio