Metal-free Lewis pairs catalysed synthesis of fluorescently labelled polyester-based amphiphilic polymers for biological imaging

Abstract

In recent years, the use of fluorescent amphiphilic polymers as the bioimaging agents has achieved significant progress, and promoted the development of the early stage cancer diagnosis and treatment. In this study, a serials of novel nitrobenzoxadiazole (NBD) fluorophore-functionalized polyester-based amphiphilic polymers were designed and synthesized via a two-step process: a hydrophobic polyester backbone was synthesized first by ring-opening alternating copolymerization (ROAC) of phthalic anhydride (PA) and allyl glycidyl ether (AGE) monomers using NBD-OH fluorophore as the initiator and metal-free Lewis pairs as the catalyst; then hydrophilic modified by three different hydrophilic pendants, PEG-SH, mercaptoacetic acid and mono-6-thio-β-cyclodextrin, through thiol-ene click reaction. Notably, directly using fluorophore as the initiator to initiate the ROAC of cyclic anhydrides and epoxides has never been reported. The influence of the feed ratio, type of Lewis pair and reaction temperature upon the polymerization performance were presented and the quantitative introduction of NBD and three kinds of hydrophilic pendants were described in detail as well. Due to the amphiphilic properties, these polymers could facilely self-assemble into fluorescent polymeric nanoparticles, which were characterized by a series of characterization techniques including surface tensiometer, dynamic light scattering (DLS), transmission electronic microscopy (TEM), and fluorescence spectroscopy. These fluorescent polymeric nanoparticles with diameters of tens or hundreds of nanometers showed good particle stability and good fluorescence performance in aqueous solution. The biocompatibility of these fluorescent polymeric nanoparticles was also excellent. In fact, the biological imaging of A549 cells could be realized successfully in the presence of the fluorescent polymeric nanoparticles. This work provides a new strategy and may inspire new approaches to the design and preparation of the biocompatible fluorescent amphiphilic polymers which could be used as the potential biological imaging agents in basic life science research and clinical applications.