Enhanced antibiotic activity of ampicillin conjugated to gold nanoparticles on PEGylated rosette nanotubes

Yiwen Fan1, Alexander C Pauer1, Arthur A Gonzales1, Hicham Fenniri1–3 1Department of Chemical Engineering, Northeastern University, Boston, MA 02115, USA; 2Department of Bioengineering, Northeastern University, Boston, MA 02115, USA; 3Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USACorrespondence: Hicham FenniriDepartment of Chemical Engineering, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USATel +1 617 373 7690Fax +1 617 373 2209Email h.fenniri@northeastern.eduPurpose: This work presents the preparation of a nanocomposite of ampicillin-conjugated gold nanoparticles (AuNPs) and self-assembled rosette nanotubes (RNTs), and evaluates its antibacterial properties against two strains of drug-resistant bacteria (Staphylococcus aureus [S. aureus], methicillin-resistant S. aureus [MRSA]).Materials and methods: Small, nearly monodisperse AuNPs (1.43±0.5 nm in diameter) nucleated on the surface of polyethylene glycol-functionalized RNTs in a one-pot reaction. Upon conjugation with ampicillin, their diameter increased to 1.86±0.32 nm. The antibacterial activity of the nanocomposite against S. aureus and MRSA was tested using different concentrations of ampicillin. The cytocompatibility of the nanocomposite was also tested against human dermal fibroblasts.Results: Based on bacterial inhibition studies, the nanocomposite demonstrated enhanced antibiotic activity against both bacterial strains. The minimum inhibitory concentration (MIC) of the nanocomposite against S. aureus was found to be 0.58 μg/mL, which was 18% lower than ampicillin alone. The nanocomposite also exhibited a 20 hrs MIC of 4 μg/mL against MRSA, approximately 10–20 times lower than previously reported values for ampicillin alone. In addition, at concentrations of 4 μg/mL of ampicillin (70 μg/mL of AuNPs), the nanocomposite showed negligible cytotoxic effects.Conclusion: Our findings offer a new approach for the treatment of drug-resistant bacteria by potentiating inhibitory effects of existing antibiotics, and delivering them using a non-toxic formulation.Keywords: ampicillin, rosette nanotubes, gold nanoparticles, S. aureus, methicillin-resistant S. aureus