In Vitro and In Vivo Demonstration of Human-Ovarian-Cancer Necrosis through a Water-Soluble and Near-Infrared-Absorbing Chlorin.
Betsy MarydasanBollapalli MadhuriShirisha CherukommuJedy JoseMambattakkara VijiSuneesh C KarunakaranTavarekere K ChandrashekarKunchala Sridhar RaoCh Mohan RaoDanaboyina RamaiahPublished in: Journal of medicinal chemistry (2018)
With the objective of developing efficient sensitizers for therapeutic applications, we synthesized a water-soluble 5,10,15,20-tetrakis(3,4-dihydroxyphenyl)chlorin (TDC) and investigated its in vitro and in vivo biological efficacy, comparing it with the commercially available sensitizers. TDC showed high water solubility (6-fold) when compared with that of Foscan and exhibited excellent triplet-excited-state (84%) and singlet-oxygen (80%) yields. In vitro photobiological investigations in human-ovarian-cancer cell lines SKOV-3 showed high photocytotoxicity, negligible dark toxicity, rapid cellular uptake, and specific localization of TDC in neoplastic cells as assessed by flow-cytometric cell-cycle and propidium iodide staining analysis. The photodynamic effects of TDC include confirmed reactive-oxygen-species-induced mitochondrial damage leading to necrosis in SKOV-3 cell lines. The in vivo photodynamic activity in nude-mouse models demonstrated abrogation of tumor growth without any detectable pathology in the skin, liver, spleen, or kidney, thereby demonstrating TDC application as an efficient and safe photosensitizer.
Keyphrases
- water soluble
- cell cycle
- photodynamic therapy
- endothelial cells
- oxidative stress
- reactive oxygen species
- induced pluripotent stem cells
- cell proliferation
- induced apoptosis
- high glucose
- cancer therapy
- mouse model
- pluripotent stem cells
- cell cycle arrest
- mass spectrometry
- solar cells
- endoplasmic reticulum stress
- signaling pathway
- quantum dots
- perovskite solar cells