title: Nanoscopic micelle delivery improves the photophysical properties and efficacy of photodynamic therapy of protoporphyrin IX.
abstract: Nanodelivery systems have shown considerable promise in increasing the solubility and delivery efficiency of hydrophobic photosensitizers for photodynamic therapy (PDT) applications. In this study, we report the preparation and characterization of polymeric micelles that incorporate protoporphyrin IX (PpIX), a potent photosensitizer, using non-covalent encapsulation and covalent conjugation methods. Depending on the incorporation method and PpIX loading percentage, PpIX existed as a monomer, dimer or aggregate in the micelle core. The PpIX state directly affected the fluorescence intensity and (1)O(2) generation efficiency of the resulting micelles in aqueous solution. Micelles with lower PpIX loading density (e.g. 0.2%) showed brighter fluorescence and higher (1)O(2) yield than those with higher PpIX loading density (e.g. 4%) in solution. However, PDT efficacy in H2009 lung cancer cells showed an opposite trend. In particular, 4% PpIX-conjugated micelles demonstrated the largest PDT therapeutic window, as indicated by the highest phototoxicity and relatively low dark toxicity. Results from this study contribute to the fundamental understanding of nanoscopic structure-property relationships of micelle-delivered PpIX and establish a viable micelle formulation (i.e. 4% PpIX-conjugated micelles) for in vivo evaluation of antitumor efficacy.
authors.affiliation: Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
authors.forename: Huiying
authors.initials: H
authors.lastname: Ding
authors.forename: Baran D
authors.initials: BD
authors.lastname: Sumer
authors.forename: Chase W
authors.initials: CW
authors.lastname: Kessinger
authors.forename: Ying
authors.initials: Y
authors.lastname: Dong
authors.forename: Gang
authors.initials: G
authors.lastname: Huang
authors.forename: David A
authors.initials: DA
authors.lastname: Boothman
authors.forename: Jinming
authors.initials: J
authors.lastname: Gao
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D006801:Humans; D008823:Micelles; D018613:Microscopy, Confocal; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry*; D011524:Protoporphyrins / Q000008:administration & dosage* / Q000494:pharmacology; D013499:Surface Properties
chemical_list: D004337:Drug Carriers; D008823:Micelles; D017319:Photosensitizing Agents; D011524:Protoporphyrins; C542623:monomethoxypolyethyleneglycol-polylactide block copolymer; D011092:Polyethylene Glycols; C028025:protoporphyrin IX