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

Abstract

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

Self-triggered click reaction in an Alzheimer's disease model:in situbifunctional drug synthesis catalyzed by neurotoxic copper accumulated in amyloid-β plaques

“…53,54 Photo-oxygenating Ab is capable of disintegrating Ab aggregates through increasing the protein polarity, which is an attractive strategy for AD therapy. [55][56][57][58] However, in the presence of Cu, just oxygenating Ab may not entirely block its brillation because Cu can still promote protein aggregation by coordinating to Ab. Considering that Cu and Ab are two critical pathogenic factors of AD, 59,60 we envisioned that in situ synthesized bifunctional drug agent with Ab-oxygenating and Cu-chelating properties could effectively disassemble Ab-Cu aggregates in vivo.…”

“…This implies that photooxygenation decreased Ab40 brillation and, possibly, toxicity, through increasing protein polarity. 56 The inhibition effect of compound 6 on Cu-accelerated Ab40 aggregation was then evaluated. Aer UV light (1 W cm À2 ) irradiation for 1 h, Ab40 monomer (10 mM) and Cu (10 mM) were incubated with 2 equiv.…”

A novel nanozyme based on selenopeptide-modified gold nanoparticles with a tunable glutathione peroxidase activity

“…Nanozymes are new articial enzymes in the combined eld of nanomaterials and enzymology research that aimed to design novel and efficient enzymatic mimics. [1][2][3] Until now, a variety of nanomaterials have been used to mimic the activity of naturally occurring enzymes, [4][5][6][7][8] such as nanocarbon materials, [9][10][11] fullerene, 12 carbon nitride, 13 Fe 3 O 4 nanoparticles, 14 mesoporous silica nanoparticles, 15 dopamine nanoparticles, 16 melanin nanoparticles, 17 and metal-organic complexes. 18 Noble metalbased nanomaterials have also shown signicant advantages as enzyme mimetics; 19,20 gold nanoparticles (AuNPs) possess excellent stability, good biocompatibility, ease of functionalization, and unique optical, and surface properties.…”

Fullerenemalonates inhibit amyloid beta aggregation, in vitro and in silico evaluation

“…This dual property of fullerenes to either quench or generate cell-damaging ROS has been applied as a cytoprotective or cytotoxic anticancer/antimicrobial/anti-Ab agent. [22][23][24][25][26] Previous reports indicated that fullerenes, and certain fullerene derivatives, inhibit Ab aggregation much more efficiently under photo-irradiation with visible light. 24,25 The dual property of C 60 to either scavenge or produce ROS has been used for a synergistic therapy for Alzheimer's disease (AD).…”

“…24,25 The dual property of C 60 to either scavenge or produce ROS has been used for a synergistic therapy for Alzheimer's disease (AD). 26 Fullerenes have two important advantages in AD research: their structure allows them to cross the blood-brain barrier 27 and they show a high capacity to inhibit Ab bril formation. 16,17,24,25,[28][29][30] However, there is controversy regarding the biocompatibility of fullerenes: some groups report nontoxic effects in different tested models, such as the LLC-PK1 proximal tubule cell model 31 or L929 mouse subcutaneous connective cells; 32 however, a high concentration of fullerenes induces toxicity in the same studies.…”