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

TLDR

Controlled activation of biomolecules is essential, yet most photoactivatable compounds require UV light, which is toxic and poorly penetrative, limiting light‑controlled bioapplications. This study aims to use NIR‑to‑UV upconversion nanoparticles as nanotransducers that absorb tissue‑penetrating NIR light and emit local UV to photoactivate caged biomolecules, especially for controlled gene expression. The authors employ NIR‑to‑UV upconversion nanoparticles that convert absorbed NIR light into emitted UV, enabling localized photoactivation of caged compounds within cells. They achieved GFP activation and knockdown, patterned activation, and deep tissue and in vivo photoactivation of caged nucleic acids, demonstrating a new level of photo‑controlled molecular delivery.

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.