Nile Blue-Based Nanosized pH Sensors for Simultaneous Far-Red and Near-Infrared Live Bioimaging

Abstract

Diblock copolymer vesicles are tagged with pHresponsive
\nNile Blue-based labels and used as a new type of
\npH-responsive colorimetric/fluorescent biosensor for far-red
\nand near-infrared imaging of live cells. The diblock copolymer
\nvesicles described herein are based on poly(2-
\n(methacryloyloxy)ethyl phosphorylcholine-block-2-
\n(diisopropylamino)ethyl methacrylate) [PMPC-PDPA]: the
\nbiomimetic PMPC block is known to facilitate rapid cell
\nuptake for a wide range of cell lines, while the PDPA block
\nconstitutes the pH-responsive component that enables facile vesicle self-assembly in aqueous solution. These biocompatible
\nvesicles can be utilized to detect interstitial hypoxic/acidic regions in a tumor model via a pH-dependent colorimetric shift. In
\naddition, they are also useful for selective intracellular staining of lysosomes and early endosomes via subtle changes in
\nfluorescence emission. Such nanoparticles combine efficient cellular uptake with a pH-responsive Nile Blue dye label to produce
\na highly versatile dual capability probe. This is in marked contrast to small molecule dyes, which are usually poorly uptaken by
\ncells, frequently exhibit cytotoxicity, and are characterized by intracellular distributions invariably dictated by their hydrophilic/
\nhydrophobic balance.