Remote activation of biomolecules in deep tissues using near-infrared-to-UV upconversion nanotransducers

Abstract

Controlled activation or release of biomolecules is very crucial in various biological applications. Controlling the activity of biomolecules have been attempted by various means and controlling the activity by light has gained popularity in the past decade. The major hurdle in this process is that photoactivable compounds mostly respond to UV radiation and not to visible or near-infrared (NIR) light. The use of UV irradiation is limited by its toxicity and very low tissue penetration power. In this study, we report the exploitation of the potential of NIR-to-UV upconversion nanoparticles (UCNs), which act as nanotransducers to absorb NIR light having high tissue penetration power and negligible phototoxicity and emit UV light locally, for photoactivation of caged compounds and, in particular, used for photo-controlled gene expression. Both activation and knockdown of GFP was performed in both solution and cells, and patterned activation of GFP was achieved successfully by using upconverted UV light produced by NIR-to-UV UCNs. In-depth photoactivation through tissue phantoms and in vivo activation of caged nucleic acids were also accomplished. The success of this methodology has defined a unique level in the field of photo-controlled activation and delivery of molecules.