Synthesis of a porphyrin with histidine-like chelate: an efficient path towards molecular PDT/SPECT theranostics.
Steven Y YapHuguette SavoieIsaline RenardBenjamin P BurkeHarry C SampleSaul Michue-SeijasStephen J ArchibaldRoss W BoyleGraeme J StasiukPublished in: Chemical communications (Cambridge, England) (2020)
The goal of "personalised" medicine has seen a growing interest in the development of theranostic agents. Bifunctional, and targeted-trifunctional, theranostic water-soluble porphyrins with a histidine-like chelating group have been synthesised via copper-catalysed azide-alkyne cycloaddition (CuAAC) "click" chemistry in high yield and purity. They are capable of photodynamic treatment and [99mTc(CO)3]+ complexation for single-photon emission computed tomography (SPECT) imaging, with a radiochemical yield of >95%. The toxicity and phototoxicity were evaluated on HT-29 cells, DU145, and DU145-PSMA cell lines, with the targeted theranostic showing more potent phototoxicity towards DU145-PSMA expressing cells.
Keyphrases
- photodynamic therapy
- pet ct
- induced apoptosis
- computed tomography
- water soluble
- fluorescence imaging
- cell cycle arrest
- cancer therapy
- oxidative stress
- positron emission tomography
- pet imaging
- signaling pathway
- high resolution
- endoplasmic reticulum stress
- magnetic resonance
- cell proliferation
- replacement therapy
- oxide nanoparticles