In Vivo Optogenetics Based on Heavy Metal-Free Photon Upconversion Nanoparticles

Photon upconversion (UC) from red or near-infrared (NIR) light to blue light is promising for in vivo optogenetics. However, the examples of in vivo optogenetics have been limited to lanthanide inorganic UC nanoparticles, and there have been no examples of optogenetics without using heavy metals. Here we show the first example of in vivo optogenetics using biocompatible heavy metal-free TTA-UC nanoemulsions. A new organic TADF sensitizer, a borondifluoride curcuminoid derivative modified with a bromo group, can promote intersystem crossing to the excited triplet state, significantly improving TTA-UC efficiency. The TTA-UC nanoparticles formed from biocompatible surfactants and methyl oleate acquire water dispersibility and remarkable oxygen tolerance. By combining with genome engineering technology using the blue light-responding photoactivatable Cre-recombinase (PA-Cre), TTA-UC nanoparticles promote Cre-reporter EGFP expression in neurons in vivo. Our results open new opportunities towards deep-tissue control of neural activities based on heavy metal-free fully organic UC systems.