Photoactivation switch from type II to type I reactions by electron-rich micelles for improved photodynamic therapy of cancer cells under hypoxia

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.
Journal of Controlled Release (Impact Factor: 7.71). 08/2011; 156(3):276-80. DOI: 10.1016/j.jconrel.2011.08.019
Source: PubMed


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.

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    • "It is preferred over surgical resection because it is noninvasive , as is the case for radiotherapy. PDT, established in the 1970s, is based on the interaction of light with photosensitive agents known as photosensitizers that preferentially accumulate in target cells and produce energy transfer and a local chemical effect (Ding et al. 2011). After exposure to specific wavelengths of light, the photosensitizer is excited from the ground state to the singlet state, then undergoes type I (electron transfer) and/or type II (energy transfer) reactions to produce reactive oxygen species (ROS), resulting in necrosis and/or apoptosis of exposed cells Pass (1993). "
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    • "Further, Zhou et al. 44 synthesized micellar nanocarriers containing pH-sensitive tetramethyl rhodamine dye which gives increased fluorescence emission within 5 minutes of pH activation, due to increased fluorophore release. Interestingly, PEG-based electron-rich micelles containing the photosensitizer 5,10,15,20-tetrakis(meso-hydroxyphenyl)porphyrin (mTHPP) synthesized by Ding et al. 45 can generate increasing amounts of O2·− by the energy transfer process, thereby competing with 1O2 production under hypoxic conditions. This results in increased photoactivation, resulting in greater phototoxicity when exposed to hypoxic cancer cells. "
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