Polydopamine Copolymers for Stable Drug Nanoprecipitation

Polydopamine (PDA), a biomaterial inspired by marine mussels, has attracted interest in cancer nanomedicine due to its photothermal properties, nanoparticle coating, and pi-pi stacking-based drug encapsulation abilities. Despite numerous one-pot and post-polymerization modifications, PDA copolymers have not been sufficiently studied in the context of stabilizing hydrophobic drugs in the process of nanoprecipitation. In this study, we tested combinatorial panels of comonomers with PDA to optimize drug loading efficiency, particle size and stability of nano formulations made via drug nanoprecipitation. As a selection criterion for optimal comonomers, we used drug aggregation-induced emission (AIE). We identified 1,1,2-Trimethyl-3-(4-sulfobutyl)benz[e]indolium (In820) as a novel and highly useful comonomer for catecholamines and optimized the conditions for its incorporation into PDA copolymers used for drug nanoprecipitation. Surprisingly, it was superior to polyethylene glycol modifications in every aspect. The leading copolymer, poly(dopamine)-poly(L-dopa)-co-In820 (PDA-PDO-In820 1:1:1), was shown to be a good stabilizer for several hydrophobic drugs. The resulting nanoparticles showed stability for up to 15 days, high encapsulation efficiency of at least 80%, low toxicity, and high antitumor efficacy in vitro. Nanoprecipitation of hydrophobic drugs can be greatly enhanced by the use of PDA copolymers containing In820, which are easy-to-prepare and highly effective stabilizers.