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

Abstract C 60 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 C 60 in one system. Herein, UCNP@C 60 ‐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@C 60 ‐pep shows protective effects against the increased oxidative stress. The ROS‐generating and ROS‐quenching abilities of UCNP@C 60 ‐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 C 60 .