Multimodal Therapeutic Approach Using Donor‐Engineered AIE Photosensitizer to Combat Multifaceted Aspects of Alzheimer's Disease

Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by cognitive decline and the accumulation of amyloid-β (Aβ) plaques, with current treatments offering only limited efficacy. Targeted photo-oxygenation of Aβ using small-molecule photosensitizers has emerged as a promising strategy to modulate amyloid aggregation and mitigate associated toxicity. In this work, the rational design and synthesis of donor-engineered, benzimidazole-functionalized aggregation-induced emission (AIE) photosensitizer with optimized photophysical and morphological properties for multimodal theranostic applications in AD is analyzed and reported. Among the synthesized probes, BI-TPA demonstrates selective binding to Aβ aggregates, effective inhibition of Aβ40 fibril formation, and efficient photo-oxygenation with minimal cytotoxicity. Comprehensive photophysical and biological studies reveal its multi-stimuli responsiveness, Fe(III) ion selectivity, rapid cellular uptake, and organelle-specific localization, along with the ability to mitigate Aβ-mediated apoptosis. Collectively, these highlights position BI-TPA as a potent multifunctional agent capable of both detection and therapeutic intervention in AD. This work presents a multifaceted design strategy for next-generation AIE-based photosensitizers, with broad implications for the development of integrated diagnostic and therapeutic platforms targeting complex neurodegenerative diseases.