3.2. Synthesis of PDA@DG3@PEG@FA NPs

Pure PDA spheres were synthesized according to previously reported protocol with slight modification [34]. Briefly, dopamine hydrochloride (100 mg, 10 mM) was dissolved in 200 mL of Milli-Q water and 1 mL of 1 M NaOH was added when the temperature of the solution reached 50 °C. Reaction was continued for 2 h followed by washing of the NPs with EtOH and Milli-Q water. Next, 6.75 mg of PDA particles were dispersed in 6 mL of TRIS buffer (pH 8.5, 10 mM) and 300 μL of PAMAM dendrimers generation 3.0 suspended in MeOH was added. After 4 h of stirring, particles were centrifuged for 10 min at 20,000 rpm at RT and washed with Milli-Q water. Immediately after the dendrimer attachment, PAMAM functionalized PDA particles were dispersed in 6 mL of borate (NaB) buffer (pH 8.5; 10 mM). Then, Mal-PEG-NHS linker was added to PDA@DG3 particle dispersion at the Mal-PEG-NHS to PAMAM wt/wt ratio of 4:1. Reaction was carried out for 1.5 h at RT followed by NaB buffer replacement with phosphate buffered saline (PBS) buffer (pH 6.8). Next, 16 mg of thiol-derivative of folic acid (SH-FA) obtained according to the literature protocol [55] was added to the suspension of PDA@DG3@PEG-Mal NPs and reaction was continued o/n in the dark. Finally, particles were collected by centrifugation and washed with Milli-Q water.