Water soluble chromenylium dyes for shortwave infrared imaging in mice

Abstract

In vivo imaging using shortwave infrared light (SWIR, 1000-2000 nm) benefits from deeper penetration depths, decreased background autofluorescence, and high resolution. However, the development of biocompatible contrast agents for these low energy wavelengths has significant challenges. While there have been significant advances in SWIR chromophore scaffolds over the past 5 years, a major barrier for widespread utility of SWIR small molecule fluorophores is their hydrophobicity and tendency to form non-emissive aggregates. Here, we report a platform for generating a panel of soluble and functional dyes for SWIR imaging by late-stage functionalization of a fluorophore intermediate via click chemistry. The resulting fluorophores with sulfonate, ammonium or zwitterion functionalities are all water soluble with bright SWIR fluorescence in serum, allowing for fast imaging in mice. Specifically, the sulfonate-carrying derivative enables clear video-rate imaging of vasculature with as little as 0.05 nmol injected dye, and the ammonium-modified dye shows strong retention in cells that enables tracking of xenograft tumor growth. We further showcase the versatility of this design by incorporating phosphonate functionalities for imaging of bone in awake and moving mice. This modular design of functional SWIR fluorophores in water provides insights for facile derivatization of existing fluorophores to introduce solubility and bioactivity towards bioimaging applications.

Bifunctional, piperazine-fused cyclic disulfides for oxidoreductase-activated cellular proagents

“…tuning probes' physicochemical properties or targeting biolocalisation. 34 Finally, in a practical sense, to promote the applications of disulfide piperazines, the streamlined 6-step protocol we report that rapidly accesses these piperazines as pure diastereomers on gram-scale will be important; as will the versatile diversification possibilities that they offer e.g. via orthogonal clickable handles.…”

Piperazine-fused cyclic disulfides: high-performance bioreduction-activated cores for bifunctional probes and reagents

“…biolocalisation targeting. 34 The utility of the cis systems for interfacing to Trx biology goes beyond probes for fundamental physiology and towards prodrugs for therapeutic targeting of inflammation, auto-immune disorders, and solid cancers, since each is closely associated with dysregulation of the central Trx redox node. The trans systems' speed and target promiscuity instead suit them for fast, traceless intracellular or triggered release, with alternative biochemical scope to current cleavable linkers (e.g.…”

Controlling the durability and optical properties of triplet–triplet annihilation upconversion nanocapsules

“…[1][2][3][4][5][6][7] Yet in each of these scenarios, it can be challenging to provide the high energy photons typically required for manipulating photochemistry, because these photons do not typically penetrate more than a few microns beyond the surface of a material due to scattering and absorption losses. 8 Two tactics are generally employed to overcome this barrier: engineering photoresponsive materials to absorb lower, more deeply penetrating wavelengths, [9][10][11][12] or generating the requisite high energy light locally using a nonlinear process. [13][14][15] Incredible gains have been made in designing low energy absorbing molecules, yet engineering photoresponsive materials can unpredictably alter other properties.…”