Chlorin e6 and Amyloid-Targeting Peptide-Conjugated Superparamagnetic Iron Oxide Nanoparticles for Synchronous Amyloid Dual-Modal Imaging and Clearance in Alzheimer’s Therapy

In recent years, multifunctional nanomaterials have emerged as a major focus of research for Alzheimer’s disease (AD) applications. Despite extensive research efforts dedicated to developing effective nanoagents, current strategies remain limited in providing robust solutions for AD prevention and treatment. Emerging studies emphasize that an ideal AD therapeutic approach should simultaneously fulfill three critical criteria: (1) precise detection of β-amyloid (Aβ) plaques, (2) effective inhibition of Aβ aggregation, and (3) successful blood–brain barrier (BBB) penetration for targeted brain delivery. However, achieving this multifunctionality remains a formidable challenge in nanomedicine. In this study, we developed Chlorin e6 (Ce6) and amyloid-targeting peptide (KLVFF)-conjugated superparamagnetic iron oxide nanoparticles (Spion-C/K) for multimodal imaging and inhibition of AD-related amyloid pathology. Spion-C/K exhibits a high binding affinity to Aβ aggregates and demonstrates excellent inhibition efficiency. Meanwhile, under the synergistic effect of photodynamics, the aggregation and amyloid toxicity inhibition efficiency of Spion-C/K on Aβ were improved. Leveraging their outstanding T 1 and T 2 magnetic resonance and fluorescence imaging properties, Spion-C and Spion-K enabled successful MR and fluorescence imaging in vitro and in vivo. Notably, Spion-C/K effectively crosses the BBB and achieves specific brain targeting, further inhibiting amyloid aggregation in vivo. These results position Spion-C/K as a promising nanotheranostic candidate that simultaneously addresses multiple critical challenges in AD management, offering possibilities for the integrated diagnosis and treatment of neurodegenerative disorders.