Responsive Contrast Agents: Synthesis and Characterization of a Tunable Series of pH-Sensitive Near-Infrared Pentamethines

ACS Omega
Virginia WyciskK Licha

Abstract

The demand for responsive dyes in optical imaging is high to achieve a better signal-to-noise ratio and, more specifically, to visualize acidic compartments of the endocytic pathway. Herein, we present a new synthetic route, with a step-by-step synthesis of water-soluble pH-sensitive cyanine dyes exhibiting pKa values in the region of physiological pH, as confirmed by absorption and fluorescence spectra. Moreover, modification of pKa values was achieved by two different substitution patterns, creating tunable pH-sensitive dyes. We demonstrated the functionality of the pH-sensitive dyes and their suitability as contrast agents for cellular uptake studies by preparing dye-labeled cetuximab and transferrin conjugates. Sulfonated head chains increased water solubility and prevented the formation of dimers, even in the context of dye-labeled bioconjugates. Confocal microscopy images of living cells revealed their pH-responsiveness, as specific fluorescence signal enhancements were observed in acidic compartments of the endocytic pathway (endosomes and lysosomes), although the background signal was low in a pH-neutral environment. Using mixtures of conjugates labeled with either a pH-sensitive or non-pH-sensitive dye for the uptake s...Continue Reading

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Citations

Jun 24, 2017·ChemistryOpen·Virginia WyciskKai Licha
Apr 11, 2017·Macromolecular Bioscience·Mathias DimdeRainer Haag
Apr 9, 2017·Langmuir : the ACS Journal of Surfaces and Colloids·Ievgen S DonskyiRainer Haag
Nov 10, 2021·Organic Letters·Donald R CaldwellMartin J Schnermann

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Methods Mentioned

BETA
fluorescence imaging
NMR
electrophoresis
surface plasmon resonance
flow cytometry
fluorescence spectroscopy
confocal microscopy
Fluorescence
chip

Software Mentioned

ctx
LAS X
Leica LAS AF
BD Accuri C6
Expasy Protparam

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