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An Integrated System to Remotely Trigger Intracellular Signal Transduction by Upconversion Nanoparticle-mediated Kinase Photoactivation
Published on: August 30, 2017
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In Vivo Optogenetics Based on Heavy Metal-Free Photon Upconversion Nanoparticles
Masanori Uji1, Jumpei Kondo1, Chikako Hara-Miyauchi2,3
1Department of Applied Chemistry, Graduate School of Engineering and Center for Molecular Systems (CMS), Kyushu University, 744 Moto-oka, Nishi-ku, Fukuoka, 819-0395, Japan.
Advanced Materials (Deerfield Beach, Fla.)
|September 23, 2024
Summary
Researchers developed heavy metal-free nanoparticles for optogenetics. These biocompatible nanoemulsions convert red light to blue light, enabling precise neural control in vivo without toxic elements.
Area of Science:
- Biomedical Engineering
- Materials Science
- Neuroscience
Background:
- Photon upconversion (UC) is crucial for in vivo optogenetics, typically using lanthanide inorganic nanoparticles.
- Current methods are limited by heavy metal use and lack of biocompatible alternatives for optogenetics.
Purpose of the Study:
- To demonstrate the first in vivo optogenetics application using biocompatible, heavy metal-free triplet-triplet annihilation upconversion (TTA-UC) nanoemulsions.
- To develop novel organic sensitizers for efficient TTA-UC and create robust, water-dispersible nanoparticles.
Main Methods:
- Synthesized a novel organic thermally activated delayed fluorescence (TADF) sensitizer (a bromo-modified boron difluoride curcuminoid derivative) to enhance intersystem crossing and TTA-UC efficiency.
- Formulated TTA-UC nanoparticles using biocompatible surfactants and methyl oleate, ensuring water dispersibility and oxygen tolerance.
- Combined TTA-UC nanoparticles with genome engineering technology (photoactivatable Cre-recombinase, PA-Cre) for blue light-mediated gene expression.
Main Results:
- Achieved efficient TTA-UC from red/NIR to blue light using the novel heavy metal-free organic sensitizer.
- Demonstrated successful Cre-reporter EGFP expression in neurons both in vitro and in vivo using the developed TTA-UC nanoparticles and PA-Cre system.
- The TTA-UC nanoparticles exhibited excellent water dispersibility and oxygen tolerance.
Conclusions:
- Established a novel heavy metal-free, fully organic TTA-UC system for in vivo optogenetics.
- This breakthrough enables deep-tissue neural activity control, opening new avenues for therapeutic interventions without relying on toxic heavy metals.
- The developed TTA-UC nanoemulsions offer a promising, biocompatible platform for advanced optogenetic applications.

