PEGylated conjugated polyelectrolytes containing 2,1,3-benzoxadiazole units for targeted cell imaging

Abstract

Two amphiphilic conjugated polyelectrolytes (CPEs) were designed and synthesized via a post-polymerization strategy. A neutral precursor polymer of poly(9,9-bis(6′-azidohexyl)fluorene-alt-2,1,3-benzoxadiazole) (PFBD-N₃) was synthesized first through Suzuki polymerization, which was followed by click reaction to incorporate dense poly(ethylene glycol) (PEG) to afford PFBD-PEG₆₀₀-COOH and PFBD-PEG₂₀₀₀-COOH, respectively. The CPEs show better solubility in water with increasing PEG chain length due to the increased hydrophilicity of longer PEG chains. Both CPEs formed nanoparticles (NPs) in water and were used as cellular probes for visualization of HT-29 cancer cells. As compared to PFBD-PEG₆₀₀-COOH NPs, PFBD-PEG₂₀₀₀-COOH NPs were less efficiently taken up by cells due to the longer PEG side chains, which significantly inhibited nonspecific cellular uptake. Further conjugation of PFBD-PEG₂₀₀₀-COOH with c(RGDfK) yielded PFBD-PEG₂₀₀₀-RGD NPs as a specific cellular probe for targeted cancer cell imaging. Preliminary study revealed that PFBD-PEG₂₀₀₀-RGD NPs were favorable for targeted cellular imaging with low cytotoxicity, high selectivity and good photostability.