Amphiphilic Perylene Bisimide-Polymer Conjugates by Cysteine-Based Orthogonal Strategy: Vesicular Aggregation, DNA Binding, and Cell Imaging

Perylene bisimides (PBIs) with high quantum yields and high chemical and photophysical stabilities are usually suffering from poor solubility in various solvents, including water, which restricts their use in biomedical and other applications. Thus, in this study, as-synthesized hydrophilic poly(1-vinylimidazole) (PVim) is introduced at both the imide positions of the hydrophobic PBI unit by using L-cysteine (Cys) bearing two orthogonally reactive groups to produce a water- and organic-soluble PBI-based polymer conjugate. To do so, first, L-cysteine is used for thiol-mediated radical polymerization of 1-vinylimidazole (Vim). In the next step, the cysteine-end-capped poly(1-vinylimidazole) (Cys-PVim) with free -NH2 is coupled with perylene-3,4,9,10-tetracarboxylic dianhydride (PDA) by employing a one-step microwave-assisted reaction to produce PBI-(Cys-PVim)(2) conjugate. The solution optical properties of this conjugate are thoroughly investigated to ascertain the extent of aggregation among PBIs units in both aqueous and organic media. The aqueous PBI-(Cys-PVim)(2) solution emits characteristic green fluorescence of PBI under UV irradiation of 365 nm wavelength. Owing to the presence of a protonable imidazole moiety, the PBI-(Cys-PVim)(2) conjugate shows pH-dependent optical properties. The amphiphilic PBI-(Cys-PVim)(2) molecules undergo self-assembly into vesicular nanostructures in water as confirmed from cryo- and high-resolution-transmission electron microscopy. The conjugate binds with ctDNA and plasmid DNA in water to form polyplexes. The fluorescent PBI-(Cys-PVim)(2) conjugate with low cytotoxicity and high quantum yield is efficiently used for the imaging of HeLa cells. The cellular uptake of the conjugate is studied at different time intervals and at different pHs using fluorescence microscopy.

Automated summary

In this study, hydrophilic poly(1-vinylimidazole) was introduced into hydrophobic perylene bisimides to produce a water- and organic-soluble polymer conjugate. The conjugate exhibited good aggregation properties in both aqueous and organic solvents, and could form complexes with DNA. Furthermore, the conjugate showed low cytotoxicity and high quantum yield, making it suitable for cellular imaging.