Reduced skin photosensitivity with meta-tetra(hydroxyphenyl)chlorin-loaded micelles based on a poly(2-ethyl-2-oxazoline)-b-poly(d,l-lactide) diblock copolymer in vivo

Mol Pharm. 2010 Aug 2;7(4):1244-53. doi: 10.1021/mp100060v.

Abstract

Photodynamic therapy (PDT) is a light-induced chemical reaction that produces localized tissue damage for the treatment of cancers and other nonmalignant conditions. The activation of photosensitizers in a target tissue is accomplished with a specific light source in the presence of molecular oxygen. In the clinic, patients treated with PDT should be kept away from direct sunlight or strong indoor lighting to avoid skin phototoxicity. In this study, a photosensitizer encapsulated within a micelle was developed to overcome this problem. The pH-sensitive micelles were successfully incorporated with meta-tetra(hydroxyphenyl)chlorin (m-THPC), and the cytotoxicity and antitumor effects were investigated in vitro and in vivo. Our results demonstrated that PDT with m-THPC-loaded micelles had no significant adverse effects on the body weight of mice in vivo. Furthermore, after an extended delivery time, m-THPC-loaded micelles and free m-THPC had similar antitumor effects, but the m-THPC-loaded micelles had less skin phototoxicity. Thus, this strategy could be used as a potential nanocarrier for PDT-mediated cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Female
  • HT29 Cells
  • Humans
  • Mesoporphyrins / chemistry
  • Mesoporphyrins / therapeutic use*
  • Mice
  • Mice, Inbred BALB C
  • Micelles*
  • Oxazoles / chemistry*
  • Photochemotherapy / methods
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / therapeutic use
  • Polyamines
  • Polyesters / chemistry*
  • Polymers / chemistry*
  • Skin / drug effects*
  • Skin / radiation effects*

Substances

  • Mesoporphyrins
  • Micelles
  • Oxazoles
  • Photosensitizing Agents
  • Polyamines
  • Polyesters
  • Polymers
  • poly(2-ethyl-2-oxazoline)
  • poly(lactide)
  • temoporfin