Nanoscopic micelle delivery improves the photophysical properties and efficacy of photodynamic therapy of protoporphyrin IX

JOURNAL OF CONTROLLED RELEASE

卷:151

Article

Ding, Huiying¹  Sumer, Baran D.³  Kessinger, Chase W.¹  Dong, Ying^1,2  Huang, Gang¹  Boothman, David A.^1,2  Gao, Jinming¹ 

[1] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA

[2] Univ Texas SW Med Ctr Dallas, Lab Mol Stress Responses, Harold C Simmons Comprehens Canc Ctr, Dallas, TX 75390 USA

[3] Univ Texas SW Med Ctr Dallas, Dept Otolaryngol Head & Neck Surg, Dallas, TX 75390 USA

关键词: Polymeric micelles;    Photodynamic therapy;    Protoporphyrin IX;    Singlet oxygen;    Photosensitizer;    Nanoparticle delivery;   

DOI  :  10.1016/j.jconrel.2011.01.004

来源: Elsevier

【 摘 要 】

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 O-1(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 O-1(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. Crown Copyright (C) 2011 Published by Elsevier B.V. All rights reserved.

【 授权许可】

Free