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

C₆₀ has a special dual function; it can act as both a powerful reactive oxygen species (ROS) producer under UV or visible light and an ROS scavenger in the dark. However, ROS has double-edged effects in living systems. It is still a great challenge for biomedical application to switch and adjust the two opposite properties of C₆₀ in one system. Herein, UCNP@C₆₀ -pep (UCNP: upconversion nanoparticle, pep: Aβ-target peptide KLVFF) is designed as a near-infrared-switchable nanoplatform for synergy therapy of Alzheimer's disease (AD). Under near-infrared (NIR) light, the Aβ-targeting hybrid nanoparticles produce ROS and result in Aβ photooxygenation, which can hinder Aβ aggregation and mitigate the attendant cytotoxicity. In the dark, UCNP@C₆₀ -pep shows protective effects against the increased oxidative stress. The ROS-generating and ROS-quenching abilities of UCNP@C₆₀ -pep are both beneficial for decreasing Aβ-induced neurotoxicity and extending the longevity of the commonly used transgenic AD model Caenorhabditis elegans CL2006. Moreover, UCNP@C60-pep can also be used for upconversion luminescence (UCL) and magnetic resonance imaging (MRI), which has benefits for "image-guided therapy." This study may offer a new perspective for the biological applications of C₆₀ .