title: Photoactivation switch from type II to type I reactions by electron-rich micelles for improved photodynamic therapy of cancer cells under hypoxia.
abstract: Photodynamic therapy (PDT) is an emerging clinical modality for the treatment of a variety of diseases. Most photosensitizers are hydrophobic and poorly soluble in water. Many new nanoplatforms have been successfully established to improve the delivery efficiency of PS drugs. However, few reported studies have investigated how the carrier microenvironment may affect the photophysical properties of photosensitizer (PS) drugs and subsequently, their biological efficacy in killing malignant cells. In this study, we describe the modulation of type I and II photoactivation processes of the photosensitizer, 5,10,15,20-tetrakis(meso-hydroxyphenyl)porphyrin (mTHPP), by the micelle core environment. Electron-rich poly(2-(diisopropylamino)ethyl methacrylate) (PDPA) micelles increased photoactivations from type II to type I mechanisms, which significantly increased the generation of O(2)(-) through the electron transfer pathway over (1)O(2) production through energy transfer process. The PDPA micelles led to enhanced phototoxicity over the electron-deficient poly(D,L-lactide) control in multiple cancer cell lines under argon-saturated conditions. These data suggest that micelle carriers may not only improve the bioavailability of photosensitizer drugs, but also modulate photophysical properties for improved PDT efficacy.
authors: Department of Pharmacology, Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390, United States.
authors: Huiying
authors: H
authors: Ding
authors: Haijun
authors: H
authors: Yu
authors: Ying
authors: Y
authors: Dong
authors: Ruhai
authors: R
authors: Tian
authors: Gang
authors: G
authors: Huang
authors: David A
authors: DA
authors: Boothman
authors: Baran D
authors: BD
authors: Sumer
authors: Jinming
authors: J
authors: Gao
mesh_terms: D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry*; D004583:Electrons; D006801:Humans; D008823:Micelles; D009369:Neoplasms / Q000188:drug therapy*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000494:pharmacology; D011109:Polymethacrylic Acids / Q000737:chemistry; D011166:Porphyrins / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D004337:Drug Carriers; D008823:Micelles; D017319:Photosensitizing Agents; D011109:Polymethacrylic Acids; D011166:Porphyrins; C511861:poly(2-(diisopropylamino)ethyl methacrylate); C437342:tetra(3-hydroxyphenyl)porphine