Non-Invasive Treatment of Alzheimer's Disease with Scintillating Nanotubes.

Effective and accessible treatments for Alzheimer's disease (AD) are urgently needed. Soluble Aβ oligomers have been identified as neurotoxic species in AD and targeted in antibody-based drug development to mitigate cognitive decline. However, controversy exists concerning their efficacy and safety. In this study, we propose an alternative strategy to inhibit the formation of Aβ oligomers by selectively oxidizing specific amino acids in the Aβ sequence, thereby preventing its aggregation. Targeted oxidation was achieved using biocompatible and blood-brain barrier-permeable multicomponent nanoscintillators that generate singlet oxygen upon X-ray interaction. Surface-modified scintillators interact selectively with Aβ and, upon X-ray irradiation, inhibit the formation of neurotoxic aggregates both in vitro and in vivo. Feeding transgenic Caenorhabditis elegans expressing human Aβ with the nanoscintillators and subsequent irradiation with soft X-ray reduced Aβ oligomer levels, extended lifespan, and restored memory and behavioral deficits. These findings support the potential of X-ray-based therapy for AD and warrant further development. This article is protected by copyright. All rights reserved.