Packing-accelerated consecutive NIR excitation (PACE) enables high energy photocatalysis and antitumor immunity in vivo

Near-infrared (NIR) photocatalysis promises deep-tissue compatibilities but remains fundamentally constrained by two bottlenecks: insufficient photon energy and rapid charge recombination. Here, we report packing-accelerated consecutive excitation (PACE), a mechanism enabling low energy near-infrared (NIR) photons to drive high energy single electron transfer (SET) reactions. We design a self-assembling ruthenium complex, Ru-3 , that forms densely packed nanoaggregates exhibiting aggregation-stabilized excited states, a pronounced excited state absorption band at ∼1315 nm, and nanosecond scale triplet lifetimes. Under dual NIR-I/IIa irradiation (808 nm/1310 nm), Ru-3 nanoparticles exhibit photophysical behavior consistent with consecutive photon harvesting and access to a higher-energy reactive state that supports efficient SET catalysis under aqueous conditions. This PACE-driven reactivity enables robust oxidation of mitochondrial NADH to NAD + , disrupting electron-transport homeostasis, inducing cGAS-STING dependent pyroptosis, and reprogramming tumor-associated macrophages toward an M1 phenotype. In multiple murine tumor models, PACE-mediated photocatalysis elicits strong antitumor immunity and leads to tumor regression with minimal systemic toxicity. This work establishes PACE as a new photochemical paradigm that overcomes the intrinsic energy and charge-separation limits of NIR photoredox chemistry, opening a route toward high-energy photocatalysis in complex biological environments.