Supramolecular photonic therapeutic agents.
A new approach to achieving selectivity for photodynamic therapy based upon the reversible off/on switching of the key therapeutic property (singlet oxygen generation) of a supramolecular photonic therapeutic agent (SPTA) in response to an external stimulus in the surrounding microenvironment is described. A series of SPTA analogues with pH responsive receptors of varying pKa are presented, in which the generation of singlet oxygen is shown to be dependent upon a proton source. For example, systems have been constructed such that the excited state energy of the photosensitizer can be decayed by a rapid photoinduced electron transfer (PET) mechanism, resulting in virtually no singlet oxygen being generated, but when the amine receptor is protonated the PET mechanism does not operate and singlet oxygen is produced. In vitro efficacy demonstrated that the SPTA derivatives can be activated within cells and one analogue is measured to have an EC50 value of 5.8 nM when assayed in the MRC5 cell line.
McDonnell
Shane O
SO
Centre for Synthesis and Chemical Biology, Conway Institute, School of Chemistry and Chemical Biology, University College Dublin, Belfield, Dublin 4, Ireland.
Hall
Michael J
MJ
Allen
Lorcan T
LT
Byrne
Annette
A
Gallagher
William M
WM
O'Shea
Donal F
DF
D001572:Benzofurans / Q000737:chemistry; D001896:Boron Compounds / Q000737:chemistry* / Q000627:therapeutic use; D004579:Electron Transport; D010084:Oxidation-Reduction; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000627:therapeutic use; D011758:Pyrroles / Q000737:chemistry* / Q000627:therapeutic use; D013379:Substrate Specificity
D001572:Benzofurans; D001896:Boron Compounds; D017319:Photosensitizing Agents; D011758:Pyrroles