Near‐Infrared Optogenetic Genome Engineering Based on Photon‐Upconversion Hydrogels

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. Herein, NIR‐light‐triggered optogenetics using biocompatible, organic TTA‐UC hydrogels is reported. To achieve triplet sensitization even in 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 heat treatment endows the excited triplets in the hydrogel with remarkable oxygen tolerance. Combined with photoactivatable Cre recombinase technology, NIR‐light stimulation successfully performs genome engineering resulting in the formation of dendritic‐spine‐like structures of hippocampal neurons. Near‐infrared (NIR) light‐triggered optogenetics with triplet–triplet annihilation‐based photon upconversion (TTA‐UC) is demonstrated. Triplet‐lifetime extension by the covalent conjugation of donor and acceptor and a heat‐induced conformational change of the hydrogel that prevents oxygen diffusion enables the formation of dendritic‐spine‐like structures by hippocampal neurons, induced by NIR‐to‐blue TTA‐UC.