In Vitro Demonstration of Apoptosis Mediated Photodynamic Activity and NIR Nucleus Imaging through a Novel Porphyrin
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- 作者：Suneesh C. Karunakaran ; P. S. Saneesh Babu ; Bollapalli Madhuri ; Betsy Marydasan ; Albish K. Paul ; Asha S. Nair ; K. Sridhar Rao ; Alagar Srinivasan ; Tavarekere K. Chandrashekar ; Ch. Mohan Rao ; Radhakrishna Pillai ; Danaboyina Ramaiah
- 刊名：ACS Chemical Biology
- 出版年：2013
- 出版时间：January 18, 2013
- 年：2013
- 卷：8
- 期：1
- 页码：127-132
- 全文大小：372K
- 年卷期：v.8,no.1(January 18, 2013)
- ISSN：1554-8937
文摘
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鈥?-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-H2DCFDA 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.