Structural Polyfluorene Derivative Nanocarriers with Promising Fluorescence Emission and Antifouling Properties

Herein, a zwitterionic PF-based copolymer, polyfluorene-a-polybenzothiadiazole-g-polycaprolactone-b-poly[3-dimethyl(methacryloxyethyl)-propaneammoniumsulfonate] [PF-a-PBTH-g-(PCL-b-PDMAPS)], was synthesized by combining multiple polymerization techniques and further quaternization. The resultant copolymer with optimized structures (P5) was able to form stabilized unimolecular micelles in an aqueous solution with a diameter of approximately 110 nm. The unique donor–acceptor structure between fluorene and benzothiadiazole group along the conjugated main chains endows copolymers with yellow-green fluorescence, while the PDMAPS chains with a unique zwitterionic nature enabled not only to enhance water solubility, drug loading efficiency (DLE), and drug loading capacity (DLC) of the whole copolymers but also to present promising antifouling property by preventing nonspecific protein/bacteria adhesion. Further in vivo and in vitro experiments demonstrate that the resultant P5 micelles also present lower cytotoxicity and efficient cellular uptake with the incubation of HeLa and HUVEC cells, which tends to prolong the circulation time of drugs. Our work not only provides a rational combination of zwitterions and polyfluorenes to significantly enhance the water solubility of hydrophobic fluorophores but also exhibits the potential of promising bioimaging for dual stimuli-responsive micelles in vitro (simulated body fluids) and in vivo (open).