Antioxidant-photosensitizer dual-loaded polymeric micelles with controllable production of reactive oxygen species

Int J Pharm. 2014 Aug 25;471(1-2):339-48. doi: 10.1016/j.ijpharm.2014.05.064. Epub 2014 Jun 2.

Abstract

Poly(ethylene glycol)-b-poly(caprolactone) (PEG-b-PCL) micelles dually loaded with both pheophorbide a (PhA) as a photosensitizer and β-carotene (CAR) as a singlet oxygen ((1)O2) scavenger were designed to control photodynamic therapy (PDT) activity in cancer treatment. The CAR in the PhA/CAR micelles significantly diminished PhA-generated (1)O2 through direct (1)O2 scavenging, whereas the CAR molecules lost their (1)O2 scavenging activity when the PhA and CAR were spatially isolated by the disintegration of the PEG-b-PCL micelles. In cell-culture systems, light irradiation at a post-treatment time that corresponded to the presence of the micelles in the blood environment induced negligible phototoxicity, whereas light irradiation at a post-treatment time that corresponded to the presence of the micelles in the intracellular environment induced remarkable phototoxicity. In addition, a longer post-treatment time induced greater internalization of PhA/CAR micelles, which resulted in higher phototoxicity, suggesting an increase in photo killing activity against the tumor cells of interest. Thus, the co-loading of a (1)O2 generator and a (1)O2 scavenger into a single micelle is a potential strategy that may be useful in facilitating more accurate and reliable PDT with site-specific controllable production of singlet oxygen species for cancer treatment.

Keywords: Antioxidant; Photodynamic therapy; Polymeric micelles; Scavenging; Singlet oxygen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Chlorophyll / administration & dosage
  • Chlorophyll / analogs & derivatives*
  • Chlorophyll / chemistry
  • Chlorophyll / pharmacology
  • Delayed-Action Preparations
  • Drug Carriers / chemistry*
  • Drug Combinations
  • Drug Compounding
  • Ethylene Glycols / chemistry*
  • Free Radical Scavengers / administration & dosage*
  • Free Radical Scavengers / chemistry
  • Free Radical Scavengers / pharmacology
  • HeLa Cells
  • Humans
  • MCF-7 Cells
  • Particle Size
  • Photochemotherapy / methods
  • Photosensitizing Agents / administration & dosage*
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacology
  • Polyesters / chemistry*
  • Reactive Oxygen Species / metabolism*
  • Surface Properties
  • beta Carotene / administration & dosage*
  • beta Carotene / chemistry
  • beta Carotene / pharmacology

Substances

  • Delayed-Action Preparations
  • Drug Carriers
  • Drug Combinations
  • Ethylene Glycols
  • Free Radical Scavengers
  • Photosensitizing Agents
  • Polyesters
  • Reactive Oxygen Species
  • poly(epsilon-caprolactone)-b-poly(ethylene glycol)
  • beta Carotene
  • Chlorophyll
  • pheophorbide a