Journal
JOURNAL OF CONTROLLED RELEASE
Volume 156, Issue 3, Pages 276-280Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2011.08.019
Keywords
Photodynamic therapy; Polymeric micelles; Nanoparticle delivery; Photoinduced electron transfer; Reactive oxygen species
Funding
- National Cancer Institute [R01CA122994, R01CA129011, R01CA102792]
- National Center for Research Resources [5 UL1 RR024982-02]
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Photodynamic therapy (PDT) is an emerging clinical modality for the treatment of a variety of diseases. Most photo-sensitizers 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 O-1(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. Published by Elsevier B.V.
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