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

Novel amphiphilic copolymers havebeen synthesized based on a biocompatiblepoly(hydroxyethylaspartamide) (PHEA) backbone, bearing both anchoringgroups for gold nanoparticles, such as thiols and disulfide, and conjugablemoieties, such as amino groups, the latter as points suitable forappending further functional agents. The strategy was to functionalizeα,β-poly[(N-2-hydroxyethyl)-d,l-aspartamide] (PHEA) with PEG2000-NH2and with ethylenediamine (EDA) obtaining a partially pegylated copolymerwith a large number of pendant primary amino groups. A fraction ofthe latter was conjugated with molecules bearing terminal thiol moietiessuch as 12-mercaptododecanoic acid (MDA) and disulfide groups suchas lipoic acid (LA), obtaining the two amphiphilic derivatives PHEA–PEG2000–EDA–MDA (PPE–MDA) and PHEA–PEG2000–EDA–LA (PPE–LA), which also provedintrinsically able to self-assemble in polymeric micelles. The twocopolymers efficiently coated gold nanostars (GNSs, size ∼40nm), wrapping around the surface increasing only slightly the hydrodynamicdiameter (reaching ∼45 nm), imparting them stability and apH-switchable surface charge, due to the unreacted amino groups. Remarkably,the poor solvation and the huge steric hindrance experienced by theamino groups lowers the observed logarithmic protonation constantsto 5.6–5.7. In vitroexperiments demonstratedthat PPE–MDA and PPE–LA copolymers have an intrinsicexcellent biocompatibility in both the human brain neuroblastoma (SH-SY5Y)and human bronchial epithelial (16-HBE) cell lines. Interaction ofthe same cell lines with “nude” GNS and GNS coated withPPE–LA was also studied, disclosing a completely satisfactorybiocompatibility of the latter. [ABSTRACT FROM AUTHOR]