Heme/NADH Mimics Co-Decorated Allosteric Capsules for Regulating Oxygen Activation and Upregulating Intracellular...

Stimuli-responsive behaviors in living bodies provide the fundamental principles for developing switchable architectures that apply to the direct function regulation. Herein, by incorporating both the µ-oxo bridged Fe^III-porphyrins and NADH (nicotinamide adenine dinucleotide) mimics into an allosteric coordination capsule, the regulation of O₂ activation and the upregulation of intracellular methionine depletion have been achieved, resulting in effective pH-activated tumor immunotherapy. Upon light irradiation, the transition from the tensed bridged Fe^III-porphyrins to the relaxed unbridged Fe^IV = O/Fe^II porphyrin pair induces unique conformational switching. The relaxed state of the capsule facilitates the binding of substrates for the oxygen atom transfer reaction. The in situ formed Fe^II-porphyrin pair, following the substrate oxygenation, activates O₂ with the intervention of NADH mimics to restore the tensed state of the capsule, thereby releasing the product for the next cycle. Regulated by the acid/base content in the system, this allostery-triggered metabolic behavior enhances the efficacy of intracellular methionine depletion therapy through the accumulation of local methionine sulfoxide, thereby improving safety. The allosteric switching strategy offers an improved approach for precise tumor treatment via dual light-and-guest stimuli-responsive regulation.