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

Abstract 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.