Hydrogen‐Bonded Organic Framework‐Based NIR‐II Activated Hydrogen Production for Treatment of Alzheimer's Disease Model Mice

Abstract Oxidative stress is the crucial pathologic factor for causing neuron death and cognitive impairment in the progression of Alzheimer's disease (AD). As a special antioxidant, molecular hydrogen (H 2 ) is responsible for alleviating oxidative stress and associated inflammatory symptoms. However, in vivo continuous and efficient hydrogen accumulation is rather difficult to realize, thus frequent dosing is required to ensure the desired therapeutic effect. Herein, hydrogen‐bonded organic frameworks (HOFs) composites are rationally designed to achieve sustainable near‐infrared II (NIR‐II) photocatalytic hydrogen evolution reaction for relieving neuroinflammation in AD model mice. The HOFs composites mainly consist of three parts: building block porphyrin as the photocatalyst, DSM (NIR‐II‐absorbing pyridinium hemicyanine dye) as fluorescent emitter, and platinum nanoparticles as co‐catalyst. Under NIR‐II laser illumination, DSM acts as an energy transducer to activate porphyrin to produce reductive hydrogen in situ. Specially, porphyrin selectively binds with the accumulated Cu ions in Aβ plaques and boosts H 2 evolution. KLVFFAED (KD8) is covalently grafted on the HOFs to improve the blood–brain barrier permeability in vivo. This designed system exhibits an admirable therapeutic effect for relieving inflammation and recovering cognitive disorder in AD model mice, thus providing a new way for exploring HOFs used for sustainable hydrogen therapy.