Mild-Temperature Synthesis of Gold Colloids with Unique Features Mediated by Polymers of Biomedical Interest

Well-defined gold nanoparticles (AuNPs) are accessible via simple synthetic methods, and their surface chemistry stands as a key factor in determining applications in the biomedical field. While macromolecules featuring amino groups are already known to successfully mediate the formation of stable gold colloids in one-pot, two-reactant, no workup reactions in aqueous media, we herein report the discovery that, under mild reaction temperatures, polymers of outstanding biomedical interest not only can play the simultaneous role of reducing and capping agent but also lead to particulate systems with unique features. From a library of samples that included branched polyethylenimine (BPEI), poly-(l-lysine) (PLL), bovine serum albumin (BSA), poly-(2-methyl-2-oxazoline) (PMeOx), poly-(<i>N</i>-(2-hydroxypropyl) methacrylamide) (PHPMA), and amine-functionalized poly-(<i>N</i>-(2-hydroxypropyl)-methacrylamide-<i>co</i>-<i>N</i>-(3-aminopropyl)-methacrylamide) P-(HPMA-<i>co</i>-APMA), we found that PHPMA end-functionalized with nitrile motifs generate spherical and stable AuNPs@PHPMA of very small size (diameter of ∼2.4 nm), as underlined by imaging experiments. Cell viability experiments indicated exceptionally good biocompatibility up to very high numerical particle concentrations as compared to the other systems. The reduced size imparted to the AuNPs@PHPMA outstanding catalytic properties (no induction time and high reaction rate constant for the hydrogenation of <i>p</i>-nitrophenol) and antimicrobial activity (total antibacterial activity against Escherichia coli and dose-dependent antibacterial activity against Staphylococcus aureus). The introduction of primary amine groups (13.4 mol %) of higher nucleophilicity known to work better for AuNP synthesis makes these unique features disappear, as evidenced for P-(HPMA-<i>co</i>-APMA). The other systems yielded 6-28 nm particles whose properties reflected both the size of the metallic core and chemical nature and conformation of the capping agent. These findings point to novel applications of PHPMA polymers worthy of further development, especially in light of their excellent water solubility and biocompatibility.