TY - JOUR
T1 - Photoactivation switch from type II to type i reactions by electron-rich micelles for improved photodynamic therapy of cancer cells under hypoxia
AU - Ding, Huiying
AU - Yu, Haijun
AU - Dong, Ying
AU - Tian, Ruhai
AU - Huang, Gang
AU - Boothman, David A.
AU - Sumer, Baran D.
AU - Gao, Jinming
N1 - Funding Information:
This research is supported by the National Cancer Institute to JG ( R01CA122994 and R01CA129011 ) and to DAB ( R01CA102792 ) and the National Center for Research Resources to BDS ( 5 UL1 RR024982-02 ). This is manuscript CSCN060 from the Program of Cell Stress and Cancer Nanomedicine in the Simmons Cancer Center. We thank Yanhong Liu at Technical Institute of Physics and Chemistry, CAS for assistance with ESR studies, Kejin Zhou for helpful discussions, and Vikram Kodibagkar and Praveen Gulaka for assistance on cell culture conditions under hypoxia.
PY - 2011/12/20
Y1 - 2011/12/20
N2 - 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 1O 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.
AB - 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 1O 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.
KW - Nanoparticle delivery
KW - Photodynamic therapy
KW - Photoinduced electron transfer
KW - Polymeric micelles
KW - Reactive oxygen species
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U2 - 10.1016/j.jconrel.2011.08.019
DO - 10.1016/j.jconrel.2011.08.019
M3 - Article
C2 - 21888934
AN - SCOPUS:82755189461
SN - 0168-3659
VL - 156
SP - 276
EP - 280
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 3
ER -