title: Diblock copolymer micelles deliver hydrophobic protoporphyrin IX for photodynamic therapy.
abstract: Polymeric micelles are emerging as an effective drug delivery system for hydrophobic photosensitizers in photodynamic therapy (PDT). The objective of this study was to investigate the formulation of hydrophobic protoporphyrin IX (PpIX) with MePEG(5000)-b-PCL(4100) [methoxy poly (ethylene glycol)-b-poly (caprolactone)] diblock copolymers and to compare their PDT response to that of free PpIX. The photophysical and photochemical properties of the polymeric PpIX micelles were studied by measuring absorbance and fluorescence spectra, PpIX-loading efficiency and stability, the micelle particle size and morphology, as well as singlet oxygen luminescence and lifetime. The spherical micelles have a high PpIX-loading efficiency of 82.4% and a narrow size distribution with a mean diameter of 52.2 +/- 6.4 nm. The cellular uptake of PpIX in RIF-1 cells using PpIX micelles was approximately two-fold higher than that for free PpIX. Free PpIX and PpIX formulated in micelles exhibited similar subcellular localization in or around the cellular plasma membrane, as demonstrated using fluorescence microscopy. In vitro PDT results showed that the PpIX micelles have markedly increased photocytotoxicity over that with free PpIX, by nearly an order of magnitude at the highest light dose used. The micelles alone had no evident phototoxicity or dark toxicity. These findings suggest that MePEG(5000)-b-PCL(4100) diblock copolymer micelles have great potential as a drug delivery system for hydrophobic photodynamic sensitizers.
authors.affiliation: Department of Medical Biophysics, University of Toronto, Ontario Cancer Institute/University Health Network, Toronto, ON, Canada.
authors.forename: Buhong
authors.initials: B
authors.lastname: Li
authors.forename: Eduardo H
authors.initials: EH
authors.lastname: Moriyama
authors.forename: Fugang
authors.initials: F
authors.lastname: Li
authors.forename: Mark T
authors.initials: MT
authors.lastname: Jarvi
authors.forename: Christine
authors.initials: C
authors.lastname: Allen
authors.forename: Brian C
authors.initials: BC
authors.lastname: Wilson
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D057927:Hydrophobic and Hydrophilic Interactions; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D010778:Photochemotherapy; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011524:Protoporphyrins / Q000737:chemistry* / Q000494:pharmacology; D013053:Spectrophotometry
chemical_list: D008823:Micelles; D011091:Polyesters; D011524:Protoporphyrins; D011092:Polyethylene Glycols; C028025:protoporphyrin IX