Controllable Dopamine Conjugation Boosts Fluorescence, Biocompatibility, and PET Imaging‐Guided Toxicity Assessment of Polycations

Abstract As well known in bioactives delivery and cancer/inflammation theranostics, polycations have recently extended their biomedical potentials in reducing visceral fat, embolizing body fluid, modulating blood coagulation, and ameliorating hyperammonemia. However, positive charges that dominate various action mechanisms, often raise risks in biosafety concerns. Also, the lack of intrinsic imaging properties of polycations makes it challenging to uncover their pharmacokinetic profiles in living objects. Herein, dopamine conjugation is demonstrated controllable and highly efficient in boosting the fluorescence or even white color emission of various polycations including hyperbranched poly(amido amine) (HPAA), polyethyleneimine and poly‐L‐lysine. By shielding partial surface positive charges, increasing hydrophobicity, and inducing aqueous self‐assembly, dopamine conjugation can significantly enhance the biocompatibility and decrease the toxicity and immunogenicity of polycations. Furthermore, the catechol‐metal binding interaction facilitates the accessibility of polycation‐based positron emission tomography (PET) probes. Different tissue uptake and biodistributions of gallium‐68‐radiolabeled HPAA before and after dopamine conjugation indicate that PET imaging can be a useful supplement to evaluate the dynamic toxicities of polycations.