Red Light Activation of Ru(II) Polypyridyl Prodrugs via Triplet-Triplet Annihilation Upconversion: Feasibility in Air and through Meat

Abstract

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/cm 2 ) 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/cm 2 ) 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.

Circularly Polarized Luminescence in Nanoassemblies: Generation, Amplification, and Application

“…Photon upconversion based on triplet-triplet annihilation (TTA-UC) is a promising approach to realize a higher-energy emission with excitation at a lower-energy light. [142][143][144][145] This process has a wide variety of applications such as solar-cell energy conversion, [94,[146][147][148] photocatalysis, [149] photodynamic therapy, [150,151] and bioimaging [152,153] due to its high efficiency, noncoherent excitation source, and tunable excitation and emission wavelengths. Generally, the mechanism of the TTA-UC process is illustrated in Figure 16A.…”

BODIPY–pyrene donor–acceptor sensitizers for triplet–triplet annihilation upconversion: the impact of the BODIPY-core on upconversion efficiency

“…Anti-Stokes luminescence based on triplet–triplet annihilation upconversion (TTA-UC) has recently attracted much interest in various applications such as biophotonics, 1–5 photovoltaics, 6–9 photochemistry, 10–14 production of solar fuels, 15 and anticounterfeiting. 16 There are two underpinning reasons motivating TTA-UC research.…”

Diastereoselective Synthesis and Two-Step Photocleavage of Ruthenium Polypyridyl Complexes Bearing a Bis(thioether) Ligand

“…2-(methylthio)ethanol (Hmte), 20,23,24 and for bidentate chelating thioether ligands. 13,25−30 Examples of the latter include combinations of thioether sulfur donors with nitrogen donor atoms, e.g. 2-(methylthio)methylpyridine (mtmp), 13 as well as symmetric bis(arylthioether) ligands, e.g.…”