Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 87, Issue -, Pages 263-273Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2016.12.081
Keywords
Photodynamic therapy (PDT); Chlorin-based photosensitizer; Pyropheophorbide-a (Pa); Phenylhydrazone; Antitumor
Funding
- National Natural Science Foundation of China [20972036, 21272048, 21471041]
- Natural Science Foundation of Heilongjiang Province [B20913]
- Program for Scientific Technological Innovation Team Construction in the Universities of Heilongjiang Province [211TD010]
- Scientific Research Fund of Heilongjiang Provincial Education Department [12531194, 12541234]
- Natural Science Youth Foundation of Heilongjiang Province [QC2016011]
- Graduate Innovation Foundation of Harbin Normal University
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Photodynamic therapy (PDT) is entering the mainstream of the cancer treatments recently. Pyropheophorbide-a (Pa), as a degradation product of chlorophyll-a, has been shown to be a potent photosensitizer in photodynamic therapy. In this paper, we investigated the in vitro photodynamic therapy of 13(1)-ortho-trifluoromethyl-phenylhydrazone modified pyropheophorbide-a (PHPa) against human HeLa cervical cancer cell line, together with ultraviolet-visible spectra, fluorescence emission spectra, stability in various solvents, and single oxygen quantum yield. The results indicated that PHPa not only showed a greater molar extinction coefficient reached 4.55 x 10(4) L mol(-1)cm(-1), the long absorption wavelength (681 nm) as we expected that makes it potential in deep tumor treatment, but also showed better stability in near neutral phosphate buffers (pH 7.4) and culture medium, as well as higher single oxygen quantum yield (Phi(D) = 40.5%) in DMF solutions. Moreover, cell experiments suggested that PHPa could be uptaken by HeLa cells successfully, and has low dark toxicity without irradiation, but remarkable photo-cytotoxicity (IC50, 1.92 +/- 0.59 mu M) that the inhibition rate of HeLa cells could increase up 91.4% at 30 mu M of PHPa after irradiation. In addition, morphological changes of HeLa cells further demonstrated that PHPa can induce damage and apoptotic cell death. Furthermore, the mechanism of photochemical processes was investigated by using specific quenching agent sodium azide (SA) and D-mannitol (DM), respectively, which showed the formation of singlet oxygen (Type II reaction mechanism) may play a predominant role, Type I and Type II photodynamic reactions could occur simultaneously in this PHPa mediated PDT process. (C) 2016 Elsevier Masson SAS. All rights reserved.
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