Understanding the growth kinetics of polydopamine nanoparticles as a function of the temperature and the type of alcohol used as solvent media in their polymerization

• According to the proposed mathematical model, the size of the PDA NPs can be predicted as a function of the polymerization time, temperature, type of alcohol used in the synthesis, and the concentration of ammonium hydroxide. • By increasing the temperature to 50 °C, it is possible to obtain PDA NPs smaller than 100 nm. • Ethanol provided greater solubility and, therefore, larger PDA NPs. • The Fe 3+ chelating capacity and antineoplastic activity of PDA NPs at 25 °C and 50 °C were similar. • If it is not necessary to obtain NPs with a diameter of less than 100 nm, they can be synthesized at room temperature without modifying their physicochemical properties, thereby saving production costs. Currently, one of the bottlenecks in the large-scale production of particles used for biomedical purposes is reproducibility achieving sizes less than 100 nm. For this reason, the main purpose of this work was to elucidate how the size of polydopamine nanoparticles (PDA NPs), which are widely used in cancer nanomedicine, was affected by several synthesis parameters to facilitate their production scaling-up. Specifically, PDA NPs growth kinetics were investigated as a function of the polymerization temperature (15–50 °C) and the type of alcohol (ethanol, 2-propanol, or a mixture of both) used to produce them, finding that an increase in temperature and the amount of 2-propanol in the solvent media allowed smaller NPs to be obtained. Based on the results achieved, a mathematical model capable of predicting PDA NP diameter as a function of the temperature and reaction time, the NH 4 OH concentration, and the type of alcohol used to synthesize them was proposed. Also, PDA solubility in the different media was studied to explain NP size behavior depending on the type of alcohol employed, which conditioned the formation of PDA oligomers. Finally, additional assays were conducted to confirm that an increase in the synthesis temperature did not affect some of the most important properties of PDA NPs from a biomedical point of view: their Fe 3+ -loading capacity and their inherent antitumor activity. Therefore, the results obtained in this research could be useful to scale-up the obtaining of 100 nm PDA NPs in a reproducible manner hereafter without significantly altering their outstanding physical-chemical properties.