Cell-Specific and pH-Activatable Rubyrin-Loaded Nanoparticles for Highly Selective Near-Infrared Photodynamic Therapy against Cancer

Spatiotemporal control of singlet oxygen (¹O₂) release is a major challenge for photodynamic therapy (PDT) against cancer with high therapeutic efficacy and minimum side effects. Here a selenium-rubyrin (NMe₂Se₄N₂)-loaded nanoparticle functionalized with folate (FA) was designed and synthesized as an acidic pH-activatable targeted photosensitizer. The nanoparticles could specifically recognize cancer cells via the FA-FA receptor binding and were selectively taken up by cancer cells via receptor-mediated endocytosis to enter lysosomes, in which NMe₂Se₄N₂ was activated to produce ¹O₂. The pH-controllable release of ¹O₂ specially damaged the lysosomes and thus killed cancer cells in a lysosome-associated pathway. The introduction of selenium into the rubyrin core enhanced the ¹O₂ generation efficiency due to the heavy atom effect, and the substitution of dimethylaminophenyl moiety at <i>meso</i>-position led to the pH-controllable activation of NMe₂Se₄N₂. Under near-infrared (NIR) irradiation, NMe₂Se₄N₂ possessed high singlet oxygen quantum yield (Φ_Δ) at an acidic pH (Φ_Δ = 0.69 at pH 5.0 at 635 nm) and could be deactivated at physiological pH (Φ_Δ = 0.06 at pH 7.4 at 635 nm). The subcellular location-confined pH-activatable photosensitization at NIR region and the cancer cell-targeting feature led to excellent capability to selectively kill cancer cells and prevent the damage to normal cells, which greatly lowered the side effects. Through intravenous injection of FA-NMe₂Se₄N₂ nanoparticles in tumor-bearing mice, tumor elimination was observed after NIR irradiation. This work presents a new paradigm for specific PDT against cancer and provides a new avenue for preparation of highly efficient photosensitizers

Biomimetic Oxygen Reduction by Cofacial Porphyrins at a Liquid–Liquid Interface

Oxygen reduction catalyzed by cofacial metalloporphyrins at the 1,2-dichlorobenzene–water interface was studied with two lipophilic electron donors of similar driving force, 1,1′-dimethylferrocene (DMFc) and tetrathiafulvalene (TTF). The reaction produces mainly water and some hydrogen peroxide, but the mediator has a significant effect on the selectivity, as DMFc and the porphyrins themselves catalyze the decomposition and the further reduction of hydrogen peroxide. Density functional theory calculations indicate that the biscobaltporphyrin, 4,5-bis­[5-(2,8,13,17-tetraethyl-3,7,12,18-tetramethylporphyrinyl)]-9,9-dimethylxanthene, Co₂(DPX), actually catalyzes oxygen reduction to hydrogen peroxide when oxygen is bound on the “exo” side (“dock-on”) of the catalyst, while four-electron reduction takes place with oxygen bound on the “endo” side (“dock-in”) of the molecule. These results can be explained by a “dock-on/dock-in” mechanism. The next step for improving bioinspired oxygen reduction catalysts would be blocking the “dock-on” path to achieve selective four-electron reduction of molecular oxygen

Self-Assembled Molecular Rafts at Liquid|Liquid Interfaces for Four-Electron Oxygen Reduction

The self-assembly of the oppositely charged water-soluble porphyrins, cobalt tetramethylpyridinium porphyrin (CoTMPyP⁴⁺) and cobalt tetrasulphonatophenyl porphyrin (CoTPPS^4–), at the interface with an organic solvent to form molecular “rafts”, provides an excellent catalyst to perform the interfacial four-electron reduction of oxygen by lipophilic electron donors such as tetrathiafulvalene (TTF). The catalytic activity and selectivity of the self-assembled catalyst toward the four-electron pathway was found to be as good as that of the Pacman type cofacial cobalt porphyrins. The assembly has been characterized by UV–visible spectroscopy, Surface Second Harmonic Generation, and Scanning Electron Microscopy. Density functional theory calculations confirm the possibility of formation of the catalytic CoTMPyP⁴⁺/ CoTPPS^4– complex and its capability to bind oxygen