Investigation of PPIX-Lipo-MnO2 to enhance photodynamic therapy by improving tumor hypoxia

Mater Sci Eng C Mater Biol Appl. 2019 Nov:104:109979. doi: 10.1016/j.msec.2019.109979. Epub 2019 Jul 16.

Abstract

The efficacy of photodynamic therapy (PDT) is reduced in the context of hypoxic environments. This is problematic, considering that hypoxia is exhibited in the vast majority of malignant tumors. Thus, increasing the concentration of oxygen in malignant tumors improves PDT treatment outcomes. Studies show that MnO2 nanoparticles can produce oxygen when it reacts with endogenous H2O2. Herein, we encapsulated Protoporphyrin IX (PPIX) in the liposome bilayer (PPIX-Lipo), which was then coated with MnO2 nanoparticles to construct PPIX-Lipo-MnO2 (PPIX-Lipo-M) in order to enhance PDT efficacy under tumor hypoxia. The PDT results show that PPIX-Lipo-M was more cytotoxic to breast cancer cells than PPIX-Lipo while under hypoxic conditions, indicating that the production of oxygen gas in hypoxic conditions improved treatment outcomes. Upon encapsulating PPIX into the liposome, the aqueous solubility of PPIX significantly improved. Consequently, the cellular uptake of both PPIX-Lipo and PPIX-Lipo-M also increased significantly compared to that of bare PPIX. Overall, PPIX-Lipo-M has the capacity to act as a therapeutic agent that relieves hypoxia and hence improve PDT efficacy.

Keywords: Cobalt chloride; Hypoxia; Liposome; MTT assay; MnO(2); Nanoparticles; Normoxia; Photodynamic therapy; Protoporphyrin IX.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Breast Neoplasms / drug therapy*
  • Cell Line, Tumor
  • Female
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Liposomes / chemistry*
  • MCF-7 Cells
  • Manganese Compounds / chemistry*
  • Nanoparticles / chemistry
  • Oxides / chemistry*
  • Oxygen / chemistry
  • Photochemotherapy / methods
  • Protoporphyrins / chemistry*
  • Protoporphyrins / pharmacology*
  • Tumor Hypoxia / drug effects*

Substances

  • Antineoplastic Agents
  • Liposomes
  • Manganese Compounds
  • Oxides
  • Protoporphyrins
  • Hydrogen Peroxide
  • protoporphyrin IX
  • Oxygen
  • manganese dioxide