Near-Infrared Switchable Fullerene-Based Synergy Therapy for Alzheimer's Disease

Area of Science:

• Nanotechnology
• Biomedical Engineering
• Neuroscience

Background:

• Fullerenes (C60) exhibit dual reactive oxygen species (ROS) properties: production under light and scavenging in the dark.
• Controlling these opposing ROS functions in a single system is challenging for biomedical applications.
• Alzheimer's disease (AD) is characterized by amyloid-beta (Aβ) aggregation and associated oxidative stress.

Purpose of the Study:

• To design a near-infrared (NIR) switchable nanoplatform (UCNP@C60-pep) for synergistic Alzheimer's disease (AD) therapy.
• To investigate the controlled ROS generation and scavenging capabilities of the nanoplatform for targeting Aβ.
• To evaluate the therapeutic efficacy and imaging potential of the nanoplatform in an AD model.

Main Methods:

• Development of upconversion nanoparticle (UCNP) core decorated with C60 and an Aβ-targeting peptide (KLVFF).
• Utilizing NIR light to trigger ROS production for Aβ photooxygenation and aggregation inhibition.
• Assessing ROS scavenging in the dark to mitigate oxidative stress.
• Evaluating therapeutic effects in a transgenic *Caenorhabditis elegans* (CL2006) AD model.
• Employing upconversion luminescence (UCL) and magnetic resonance imaging (MRI) for image-guided therapy.

Main Results:

• UCNP@C60-pep successfully produced ROS under NIR light, inhibiting Aβ aggregation and reducing cytotoxicity.
• The nanoplatform demonstrated ROS-scavenging properties in the dark, offering protection against oxidative stress.
• Both ROS-generating and scavenging functions were beneficial in decreasing Aβ-induced neurotoxicity and extending lifespan in the AD model.
• The nanoplatform exhibited potential for UCL and MRI, enabling image-guided therapeutic applications.

Conclusions:

• The developed UCNP@C60-pep nanoplatform offers a novel NIR-switchable approach for synergistic AD therapy.
• Controlled modulation of ROS by the nanoplatform effectively targets Aβ pathology and oxidative stress.
• This study provides a new perspective for the biological applications of C60-based nanomaterials in neurodegenerative diseases.