2021 journal article

Single-Fluorophore Single-Chain Nanoparticle Undergoes Fluorophore-Driven Assembly with Fluorescence Features Retained in Physiological Milieu

ACS APPLIED POLYMER MATERIALS, 3(4), 1767–1776.

co-author countries: United States of America 🇺🇸
author keywords: single-chain nanoparticle; amphiphilic; hydrophobic fluorophore; unimer; fluorescence; physiological milieu
Source: Web Of Science
Added: June 10, 2021

To address the longstanding problem of solubilization of hydrophobic fluorophores in aqueous solution, a recent design employed a single fluorophore attached to the terminus of a heterotelechelic, amphiphilic polymer that contained poly(ethylene glycol) (PEG), dodecyl, and sulfonate pendant groups (1:1:5 ratio). The resulting single-polymer–single-fluorophore construct folded in aqueous solution containing 1 M NaCl but is shown here to comprise a mixture of folded (i.e., unimer) and unfolded species in low ionic strength media (e.g., phosphate-buffered saline, PBS) characteristic of physiological milieu. To identify molecular designs that engender unimer formation in PBS solution, heterotelechelic amphiphilic polymers containing cyclododecyl (rather than PEG and dodecyl) and sulfonate pendant groups were synthesized via reversible addition-fragmentation chain-transfer polymerization with variation in (1) degree of polymerization (weight average molecular weight 10–34 kDa) and (2) ratios of pendant groups. A perylene-monoimide or chlorin was used as the hydrophobic fluorophore and attached to the polymer via a maleimide group. Unimer formation occurred quantitatively in PBS solution with polymers of ≥28 kDa, a ratio of cyclododecyl/sulfonate groups of 1:4 to 1:6, and an attached hydrophobic fluorophore. The hydrophobic fluorophore promoted folding of the attached polymer, thereby driving its own encapsulation even in low ionic strength media. The resulting single-chain nanoparticles bearing a single fluorophore in PBS solution retain a fluorescence quantum yield that is at least 70% of that of the hydrophobic fluorophore benchmark alone in a nonpolar solvent. The molecular designs presented herein appear well suited for aqueous solubilization of hydrophobic fluorophores in life science applications.