Red Light Activation of Ru(II) Polypyridyl Prodrugs via Triplet-Triplet Annihilation Upconversion: Feasibility in Air and through Meat.
Triplet-triplet annihilation upconversion (TTA-UC) is a promising photophysical tool to shift the activation wavelength of photopharmacological compounds to the red or near-infrared wavelength domain, in which light penetrates human tissue optimally. However, TTA-UC is sensitive to dioxygen, which quenches the triplet states needed for upconversion. Here, we demonstrate not only that the sensitivity of TTA-UC liposomes to dioxygen can be circumvented by adding antioxidants, but also that this strategy is compatible with the activation of ruthenium-based chemotherapeutic compounds. First, red-to-blue upconverting liposomes were functionalized with a blue-light sensitive, membrane-anchored ruthenium polypyridyl complex, and put in solution in presence of a cocktail of antioxidants composed of ascorbic acid and glutathione. Upon red light irradiation with a medical grade 630 nm PDT laser, enough blue light was produced by TTA-UC liposomes under air to efficiently trigger full activation of the Ru-based prodrug. Then, the blue light generated by TTA-UC liposomes under red light irradiation (630 nm, 0.57 W/cm²) through different thicknesses of pork or chicken meat was measured, showing that TTA-UC still occurred even beyond 10 mm of biological tissue. Overall, the rate of activation of the ruthenium compound in TTA-UC liposomes using either blue or red light (1.6 W/cm²) through 7 mm of pork fillet were found comparable, but the blue light caused significant tissue damage, whereas red light did not. Finally, full activation of the ruthenium prodrug in TTA-UC liposomes was obtained under red light irradiation through 7 mm of pork fillet, thereby underlining the in vivo applicability of the activation-by-upconversion strategy.
Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, Leiden 2333 CC, The Netherlands. s.h.c.askes@chem.leidenuniv.nl.
Sven H C
SH
Askes
Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, Leiden 2333 CC, The Netherlands. m.s.meijer@chem.leidenuniv.nl.
Michael S
MS
Meijer
Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, Leiden 2333 CC, The Netherlands. tessel.bouwens@student.uva.nl.
Tessel
T
Bouwens
Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, Leiden 2333 CC, The Netherlands. iris.landman@student.uva.nl.
Iris
I
Landman
Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, Leiden 2333 CC, The Netherlands. bonnet@chem.leidenuniv.nl.
Sylvestre
S
Bonnet
D000388:Air; D000818:Animals; D002645:Chickens; D004735:Energy Transfer; D031541:Fluorescence Resonance Energy Transfer; D008027:Light; D008081:Liposomes / Q000737:chemistry*; D008460:Meat; D015394:Molecular Structure; D055668:Photochemical Processes; D011355:Prodrugs / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry*; D013552:Swine
D008081:Liposomes; D011355:Prodrugs; D012428:Ruthenium
liposomes; meat spectroscopy; photochemical upconversion; phototherapy; ruthenium prodrugs