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

• Published in: Angewandte Chemie International Edition Vol. 61; no. 2; pp. e202109068 - n/a
• Main Authors: Zhang, Haochen, Yu, Dongqin, Liu, Shuting, Liu, Chun, Liu, Zhenqi, Ren, Jinsong, Qu, Xiaogang
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 10.01.2022
• Edition: International ed. in English
• Subjects: Alzheimer's disease; Animal models; Blood-brain barrier; Catalysts; Energy transfer; Fluorescence; Fluorescence resonance energy transfer; hydrogen-bonded organic frameworks; In vivo methods and tests; Irradiation; Membrane permeability; Neurodegenerative diseases; Oxidation; Peptides; photo-oxygenation; Photon absorption; Photons; Phototherapy; Porphyrins; Pyridinium; Radiation; second near-infrared; Selectivity; Senile plaques; Singlet oxygen; β-Amyloid; β-amyloids; second near-infrared; hydrogen-bonded organic frameworks; photo-oxygenation; Alzheimer's disease; β-amyloids
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.202109068

Phototherapy has emerged as a powerful approach for interrupting β‐amyloid (Aβ) 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 (1O2) for Aβ 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 Aβ selectivity. The HOF‐based photooxygenation catalyst shows an outstanding inhibitory effect of Aβ aggregation upon the NIR‐II irradiation. Further in vivo studies demonstrate the obvious decrease of craniocerebral Aβ plaques and recovery of memory deficits in triple‐transgenic AD (3×Tg‐AD) model mice. NIR‐II hydrogen‐bonded organic frameworks (HOFs) were devised to oxidize β‐amyloid spatiotemporally and noninvasively. The well‐designed photocatalyst shows an inhibitory effect of Aβ aggregation and recovery of memory deficits in triple‐transgenic AD model mice upon the NIR‐II irradiation.