In Vitro Demonstration of Apoptosis Mediated Photodynamic Activity and NIR Nucleus Imaging through a Novel Porphyrin

被引：79

作者：

Karunakaran, Suneesh C. ^{[1
]}

Babu, P. S. Saneesh ^{[2
]}

Madhuri, Bollapalli ^{[3
]}

Marydasan, Betsy ^{[1
]}

Paul, Albish K. ^{[1
]}

Nair, Asha S. ^{[2
]}

Rao, K. Sridhar ^{[3
]}

Srinivasan, Alagar ^{[4
]}

Chandrashekar, Tavarekere K. ^{[4
]}

Rao, Ch. Mohan ^{[3
]}

Pilai, Radhakrishna ^{[2
]}

Ramaiah, Danaboyina ^{[1
]}

机构：

[1] CSIR, NIIST, Chem Sci & Technol Div, Trivandrum 695019, Kerala, India

[2] Rajiv Gandhi Ctr Biotechnol, Trivandrum 695014, Kerala, India

[3] CCMB, CSIR, Hyderabad 500007, Andhra Pradesh, India

[4] NISER, Bhubaneswar 751005, Odisha, India

来源：

ACS CHEMICAL BIOLOGY | 2013年 / 8卷 / 01期

关键词：

DNA-BINDING; THERAPY; PHOTOSENSITIZERS; PHOTOFRIN; YIELDS;

D O I：

10.1021/cb3004622

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We synthesized a novel water-soluble porphyrin THPP and its metalated derivative Zn-THPP having excellent triplet excited state quantum yields and singlet oxygen generation efficiency. When compared to U.S. Food and Drug Administration approved and clinically used sensitizer Photofrin, THPP showed ca. 2-3-fold higher in vitro photodynamic activity in different cell lines under identical conditions. The mechanism of the biological activity of these porphyrin systems has been evaluated through a variety of techniques: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, comet assay, poly(ADP-ribose)-polymerase (PARP) cleavage, CM-H(2)DCFDA assay, DNA fragmentation, flow cytometric analysis, fluorescence, and confocal microscopy, which confirm the apoptotic cell death through predominantly reactive oxygen species (ROS). Moreover, THPP showed rapid cellular uptake and are localized in the nucleus of the cells as compared to Hoechst dye and Photofrin, thereby demonstrating its use as an efficient sensitizer in photodynamic therapy and live cell NIR nucleus imaging applications.

引用

页码：127 / 132

页数：6

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