Chlorin Endogenous to the North Pacific Brittle Star Ophiura sarsii for Photodynamic Therapy Applications in Breast Cancer and Glioblastoma Models.
Antonina KlimenkoElvira E RodinaDenis SilachevMaria BegunValentina A BabenkoAnton S BenditkisAnton S KozlovAlexander A KrasnovskyYuri S KhotimchenkoVladimir L KatanaevPublished in: Biomedicines (2022)
Photodynamic therapy (PDT) represents a powerful avenue for anticancer treatment. PDT relies on the use of photosensitizers-compounds accumulating in the tumor and converted from benign to cytotoxic upon targeted photoactivation. We here describe (3 S ,4 S )-14-Ethyl-9-(hydroxymethyl)-4,8,13,18-tetramethyl-20-oxo-3-phorbinepropanoic acid (ETPA) as a major metabolite of the North Pacific brittle stars Ophiura sarsii . As a chlorin, ETPA efficiently produces singlet oxygen upon red-light photoactivation and exerts powerful sub-micromolar phototoxicity against a panel of cancer cell lines in vitro. In a mouse model of glioblastoma, intravenous ETPA injection combined with targeted red laser irradiation induced strong necrotic ablation of the brain tumor. Along with the straightforward ETPA purification protocol and abundance of O. sarsii , these studies pave the way for the development of ETPA as a novel natural product-based photodynamic therapeutic.
Keyphrases
- photodynamic therapy
- cancer therapy
- mouse model
- fluorescence imaging
- tertiary care
- randomized controlled trial
- high glucose
- diabetic rats
- high dose
- childhood cancer
- oxidative stress
- drug induced
- young adults
- antibiotic resistance genes
- endothelial cells
- mass spectrometry
- radiation induced
- atrial fibrillation
- combination therapy
- high resolution
- high speed
- case control
- catheter ablation