NIR-II Hydrogen-Bonded Organic Frameworks (HOFs) Used for Target-Specific Amyloid-b Photooxygenation in an Alzheimer's Disease Model

Zhang, HC; Yu, DQ; Liu, ST; Liu, C; Liu, ZQ; Ren, JS; Qu, XG

Abstract

Phototherapy has emerged as a powerful approach for interrupting beta-amyloid (A beta) self-assembly. However, deeper tissue penetration and safer photosensitizers are urgent to be exploited for avoiding damaging nearby normal tissues and improving therapeutic effectiveness. A hydrogen-bonded organic framework (HOF)-based NIR-II photooxygenation catalyst is presented here to settle the abovementioned challenges. By encapsulating the pyridinium hemicyanine dye DSM with a large two-photon absorption (TPA) cross-section in NIR-II window into the porphyrin-based HOF, the resultant DSM@n-HOF-6 exhibits significant two-photon NIR-II-excited Fluorescence Resonance Energy Transfer (FRET) to generate singlet oxygen (O-1(2)) for A beta oxidation. Further, the target peptides of KLVFFAED (KD8) are covalently grafted on DSM@n-HOF-6 to enhance the blood-brain barrier (BBB) permeability and A beta selectivity. The HOF-based photooxygenation catalyst shows an outstanding inhibitory effect of A beta aggregation upon the NIR-II irradiation. Further in vivo studies demonstrate the obvious decrease of craniocerebral A beta plaques and recovery of memory deficits in triple-transgenic AD (3 X Tg-AD) model mice.

Keywords: Alzheimer's disease; hydrogen-bonded organic frameworks; photo-oxygenation; second near-infrared; beta-amyloids

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Hydrogen-bonded Organic Framework (HOF) Materials

Hydrogen-bonded organic frameworks (HOFs) are molecular structures that could be used to treat Alzheimer's disease. HOF is an organic molecular network formed by hydrogen bond interactions with a highly controllable pore structure, which is expected to be used for drug delivery and embedding of drug molecules. Its unique structure provides a stable carrier for drug molecules and enables the gradual release of drugs through microscopic pores. HOF also has good biocompatibility and is expected to reduce drug side effects. This innovative organic framework provides new potential avenues for the treatment of Alzheimer's disease, potentially improving drug efficacy and bioavailability.