Cascade catalytic nanoplatform for enhanced starvation and sonodynamic therapy

J Drug Target. 2020 Feb;28(2):195-203. doi: 10.1080/1061186X.2019.1641507. Epub 2019 Aug 1.

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.

Keywords: Catalytic reaction; magnetic resonance imaging; manganese dioxide nanoparticles; sonodynamic therapy; starvation therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Catalysis
  • Cell Line, Tumor
  • Glucose Oxidase / metabolism
  • Hematoporphyrins / chemistry
  • Humans
  • Hydrogen Peroxide / metabolism
  • Magnetic Resonance Imaging
  • Manganese Compounds / chemistry
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanoparticles*
  • Neoplasms / therapy*
  • Oxides / chemistry
  • Oxygen / metabolism*
  • Ultrasonic Therapy / methods*

Substances

  • Hematoporphyrins
  • Manganese Compounds
  • Oxides
  • hematoporphyrin monomethyl ether
  • manganese oxide
  • Hydrogen Peroxide
  • Glucose Oxidase
  • Oxygen