NIR-responsive upconversion nanoplatforms: an anionic drug carrier for ROS amplification induced by β-amyloid fibrils

Area of Science:

• Biomaterials Science
• Nanotechnology
• Neuroscience

Background:

• Alzheimer's disease (AD) is characterized by amyloid-beta (Aβ) misfolding and aggregation, posing a significant global health challenge.
• Polyoxometalates (POMs) show promise in degrading Aβ fibrils and inhibiting fibrillation.
• Targeted reactive oxygen species (ROS) amplification is crucial for effective AD photodynamic therapy.

Purpose of the Study:

• To develop a chitosan-modified, near-infrared (NIR)-responsive upconversion nanoplatform for targeted POM delivery.
• To enhance ROS generation for improved therapeutic efficacy against Aβ fibrils.
• To investigate the potential of this nanoplatform for Alzheimer's disease photooxidative treatment.

Main Methods:

• Fabrication of a nanoplatform by modifying upconversion nanoparticles (UCNPs) with silica, GPS linker, and chitosan (CH).
• Loading of anionic POMs onto the cationic CH layer via electrostatic interactions.
• NIR irradiation to trigger photodynamic ROS generation and assess its effect on Aβ fibrils.

Main Results:

• The nanoplatform demonstrated efficient POM loading (415.41 μg mg⁻¹) dependent on CH modification.
• NIR irradiation induced significant ROS generation, which was approximately doubled in the presence of Aβ fibrils.
• The system showed enhanced targeted therapeutic efficacy against Aβ fibrils.

Conclusions:

• The developed nanoplatform effectively delivers POMs and amplifies ROS under NIR irradiation.
• Targeted ROS generation shows enhanced efficacy against Aβ fibrils, offering a novel strategy for AD photooxidative treatment.
• This system provides insights into designing chitosan-modified upconversion nanoparticle-based drug carriers.