Amphiphilic Copolymers Based on Poly[(hydroxyethyl)-d,l-aspartamide]: A Suitable Functional Coating for Biocompatible Gold Nanostars

Novel amphiphilic copolymers have been synthesized based on a biocompatible p o l y - (hydroxyethylaspartamide) (PHEA) backbone, bearing both anchoring groups for gold nanoparticles, such as thiols and disulfide, and conjugable moieties, such as amino groups, the latter as points suitable for appending further functional agents. The strategy was to functionalize α,β-poly[(N-2- hydroxyethyl)-D,L-aspartamide] (PHEA) with PEG2000-NH2 and with ethylenediamine (EDA) obtaining a partially pegylated copolymer with a large number of pendant primary amino groups. A fraction of the latter was conjugated with molecules bearing terminal thiol moieties such as 12-mercaptododecanoic acid (MDA) and disulfide groups such as lipoic acid (LA), obtaining the two amphiphilic derivatives PHEA−PEG2000−EDA−MDA (PPE−MDA) and PHEA−PEG2000−EDA−LA (PPE−LA), which also proved intrinsically able to self-assemble in polymeric micelles. The two copolymers efficiently coated gold nanostars (GNSs, size ∼40 nm), wrapping around the surface increasing only slightly the hydrodynamic diameter (reaching ∼45 nm), imparting them stability and a pH-switchable surface charge, due to the unreacted amino groups. Remarkably, the poor solvation and the huge steric hindrance experienced by the amino groups lowers the observed logarithmic protonation constants to 5.6−5.7. In vitro experiments demonstrated that PPE−MDA and PPE−LA copolymers have an intrinsic excellent biocompatibility in both the human brain neuroblastoma (SH-SY5Y) and human bronchial epithelial (16-HBE) cell lines. Interaction of the same cell lines with “nude” GNS and GNS coated with PPE−LA was also studied, disclosing a completely satisfactory biocompatibility of the latter.