Yingjie Zhang1, Huiling Wang2, Xuedong Jia1, Shuzhang Du1, Yanyan Yin3, Xiaojian Zhang1. 1. Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. 2. School of Pharmaceutical Sciences, Zhengzhou Railway Vocational and Technical College, Zhengzhou, China. 3. School of Pharmacy, Xinxiang Medical University, Xinxiang, China.
Abstract
Background: Sonodynamic therapy (SDT) has emerged as an alternative to the traditional treatments of cancer. However, the oxygen consumption induced by SDT and glucose oxidase (GOx) mediated starvation therapy would worsen the hypoxic tumor environment, which further impeded therapeutic efficacy. Purpose: To develop a nanoplatform and investigate its anti-cancer mechanism for enhanced starvation and SDT. Methods: We constructed a cascade catalytic nanoplatform based on GOx modified the mesoporous MnO2 NPs loaded with hematoporphyrin monomethyl ether (HMME), which were designated as GOx-MnO2/HMME. We characterized them for their catalytic activity, and investigate the magnetic resonance imaging and anti-tumor efficiency in vitro and in vivo. Results: MnO2 NPs with catalase-like activity could oxidize H2O2 under acid condition to produce O2, which not only in turn was supplied to the glucose-depletion reaction for an efficient starvation therapy, but also enhanced the 1O2 generation for HMME mediated SDT effect. In addition, the released Mn2+ ions in the system were able to enhance the MRI signal. Both in vitro and in vivo experiments suggested the cascade catalytic-therapeutic effect between GOx, MnO2 NPs and HMME, demonstrating the enhanced starvation and SDT.
Background: Sonodynamic therapy (SDT) has emerged as an alternative to the traditional treatments of cancer. However, the oxygen consumption induced by SDT and glucose oxidase (GOx) mediated starvation therapy would worsen the hypoxic tumor environment, which further impeded therapeutic efficacy. Purpose: To develop a nanoplatform and investigate its anti-cancer mechanism for enhanced starvation and SDT. Methods: We constructed a cascade catalytic nanoplatform based on GOx modified the mesoporous MnO2 NPs loaded with hematoporphyrin monomethyl ether (HMME), which were designated as GOx-MnO2/HMME. We characterized them for their catalytic activity, and investigate the magnetic resonance imaging and anti-tumor efficiency in vitro and in vivo. Results: MnO2 NPs with catalase-like activity could oxidize H2O2 under acid condition to produce O2, which not only in turn was supplied to the glucose-depletion reaction for an efficient starvation therapy, but also enhanced the 1O2 generation for HMME mediated SDT effect. In addition, the released Mn2+ ions in the system were able to enhance the MRI signal. Both in vitro and in vivo experiments suggested the cascade catalytic-therapeutic effect between GOx, MnO2 NPs and HMME, demonstrating the enhanced starvation and SDT.