1.
In Vivo Optogenetics Based on Heavy Metal-Free Photon Upconversion Nanoparticles.
Abstract:
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 the first example of in vivo optogenetics using biocompatible heavy metal-free TTA-UC nanoemulsions is shown. A new organic TADF sensitizer, a boron difluoride 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 vitro and in vivo. The results open new opportunities toward deep-tissue control of neural activities based on heavy metal-free fully organic UC systems.
2.
Near-infrared optogenetic genome engineering based on photon upconversion hydrogels.
Abstract:
Photon upconversion (UC) from near-infrared (NIR) light to visible light has enabled optogenetic manipulations in deep tissues. However, materials for NIR optogenetics have been limited to inorganic UC nanoparticles. Extension to organic triplet-triplet annihilation (TTA)-based UC systems would innovate NIR optogenetics toward the use of biocompatible materials placed at a desired position. Here, we report the first example of NIR light-triggered optogenetics by using TTA-UC hydrogels. To achieve triplet sensitization even in the highly viscous hydrogel matrices, a NIR-absorbing complex is covalently linked with energy-pooling acceptor chromophores, which significantly elongates the donor triplet lifetime. The donor and acceptor are solubilized in hydrogels formed from biocompatible Pluronic F127 micelles, and we find that the additional heat treatment endows remarkable oxygen-tolerant property to the excited triplets in the hydrogel. Combined with photoactivatable Cre recombinase (PA-Cre) technology, NIR light stimulation successfully performs genome engineering such as hippocampal dendritic spine formation involved in learning and long-term memory.
