Biomimetic Chlorosomes: Oxygen-Independent Photocatalytic Nanoreactors for Efficient Combination Photoimmunotherapy

Abstract

Photocatalytic therapy for hypoxic tumors often suffers from inefficiencies due to its dependence on oxygen and the risk of uncontrolled activation. Inspired by the oxygen-independent and precisely regulated photocatalytic functions of natural light-harvesting chlorosomes, chlorosome-mimetic nanoreactors, termed Ru-Chlos, are engineered by confining the aggregation of photosensitive ruthenium-polypyridyl-silane monomers. These Ru-Chlos exhibit markedly enhanced photocatalytic performance compared to their monomeric counterparts under acidic conditions, while notably bypassing the consumption of oxygen or hydrogen peroxide. The photocatalytic activity of Ru-Chlos is finely tunable through light-responsive disassembly of the Ru-bridged matrix, with tunability governed by pre-irradiation duration. Utilization of Ru-Chlos loading prodrug [2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)] (ABTS) for phototherapy facilitates the generation of toxic radicals (oxABTS) and the photocatalytic conversion of endogenous NADH to NAD⁺, inducing oxidative stress in hypoxic cancer cells. Simultaneously, the light-responsive degradation of Ru-Chlos produces Ru-based toxins that further contribute to the therapeutic effect. This dual-action mechanism elicits potent immunogenic cell death effects and significantly enhances antitumor efficacy with the aid of a PD-l blockade. These biomimetic chlorosomes highlight their potential to advance oxygen-independent photocatalytic nanoreactors with controlled activity for novel cancer photoimmunotherapy strategies.