We describe two water‐soluble ruthenium complexes, [1]Cl₂ and [2]Cl₂, that photodissociate to release a cytotoxic nicotinamide phosphoribosyltransferase (NAMPT) inhibitor with a low dose (21 J cm⁻²) of red light in an oxygen‐independent manner. Using a specific NAMPT activity assay, up to an 18‐fold increase in inhibition potency was measured upon red‐light activation of [2]Cl₂, while [1]Cl₂ was thermally unstable. For the first time, the dark and red‐light‐induced cytotoxicity of these photocaged compounds could be tested under hypoxia (1 % O₂). In skin (A431) and lung (A549) cancer cells, a 3‐ to 4‐fold increase in cytotoxicity was found upon red‐light irradiation for [2]Cl₂, whether the cells were cultured and irradiated with 1 % or 21 % O₂. These results demonstrate the potential of photoactivated chemotherapy for hypoxic cancer cells, in which classical photodynamic therapy, which relies on oxygen activation, is poorly efficient.

Light upconversion is a very powerful tool in bioimaging as it can eliminate autofluorescence, increase imaging contrast, reduce irradiation damage, and increase excitation penetration depth in vivo. In particular, triplet–triplet annihilation upconverting (TTA‐UC) nanoparticles and liposomes offer high upconversion efficiency at low excitation power. However, TTA‐UC is quenched in air by oxygen, which also leads to the formation of toxic singlet oxygen. In this work, polyisobutylene‐monomethyl polyethylene glycol block copolymers are synthesized and used for preparing polymersomes that upconvert red light into blue light in absence of oxygen. In addition, it is demonstrated that biocompatible antioxidants such as l‐ascorbate, glutathionate, l‐histidine, sulfite, trolox, or even opti‐MEM medium, can be used to protect the TTA‐UC process in these polymersomes resulting in red‐to‐blue upconversion under aerobic conditions. Most importantly, this approach is also functional in living cells. When A549 lung carcinoma cells are treated with TTA‐UC polymersomes in the presence of 5 × 10⁻³ m ascorbate and glutathionate, upconversion in the living cells is one order of magnitude brighter than that observed without antioxidants. These results propose a simple chemical solution to the issue of oxygen sensitivity of TTA‐UC, which is of paramount importance for the technological advancement of this technique in biology.

Light‐activated ruthenium polypyridyl anticancer prodrugs often suffer from poor water solubility, poor selectivity, and/or ill‐defined intracellular targets. Coordination of the d‐ or l‐glucose thioether ligand 3 (2‐(2‐(2‐(methylthio)ethoxy)ethoxy)ethyl‐β‐glucopyranoside) to the highly lipophilic ruthenium complex [Ru(tpy)(dppn)(H₂O)]²⁺ ([1]²⁺; dppn=benzo[i]dipyrido‐[3,2‐a:2′,3′‐c]phenazine, tpy=2,2′:6′,2′′‐terpyridine) solved all these problems at once. The two enantiomers of [Ru(tpy)(dppn)(3)][PF₆]₂, [d‐2][PF₆]₂ and [l‐2][PF₆]₂, were soluble in water, which allowed the influence of the chirality of the glucose moiety on uptake, toxicity, and intracellular localization of the prodrug to be probed without changing any other physicochemical properties. Both compounds showed mild, but different, cytotoxicity in A549 (human lung carcinoma) and MCF‐7 (human breast adenocarcinoma) cancer cells in the dark, whereas following low doses of visible light irradiation (3.1 J cm⁻² at λ = 454 nm), a similar, but high cytotoxicity (EC₅₀ < 1 μm), was observed. Irrespective of the chirality, both slightly emissive Ru complexes were found in the mitochondria, and two modes of action may contribute to light‐induced cell death: 1) the glucose thioether ligand is photosubstituted by water, thus [1]²⁺, which interacts with DNA at an exceptionally high 400:1 base pair/Ru ratio, is released; 2) both [1]²⁺ and [2]²⁺ produce massive amounts of singlet oxygen, which leads to very efficient photodynamic DNA cleavage.

Anthropogenic climate change urgently calls for the greening and intensification of the chemical industry. Most chemical reactors make use of catalysts to increase their conversion yields, but their operation at steady-state temperatures limits their rate, selectivity, and energy efficiency. Here, we show how to break such a steady-state paradigm using ultrashort light pulses and photothermal nanoparticle arrays to modulate the temperature of catalytic sites at timescales typical of chemical processes. Using heat dissipation and time-dependent microkinetic modeling for a number of catalytic landscapes, we numerically demonstrate that pulsed photothermal catalysis can result in a favorable, dynamic mode of operation with higher energy efficiency, higher catalyst activity than for any steady-state temperature, reactor operation at room temperature, resilience against catalyst poisons, and access to adsorbed reagent distributions that are normally out of reach. Our work identifies the key experimental parameters controlling reaction rates in pulsed heterogeneous catalysis and provides specific recommendations to explore its potential in real experiments, paving the way to a more energy-efficient and process-intensive operation of catalytic reactors.