Molecular Aspects of the Interaction with Gram-Negative and Gram-Positive Bacteria of Hydrothermal Carbon Nanoparticles Associated with Bac8c2,5Leu Antimicrobial Peptide

Giulia Barzan; Ida Kokalari; Giacomo Gariglio; Elena Ghibaudi; Marc Devocelle; Marco P Monopoli; Alessio Sacco; Angelo Greco; Andrea M Giovannozzi; Andrea M Rossi; Ivana Fenoglio

doi:10.1021/acsomega.2c00305

Molecular Aspects of the Interaction with Gram-Negative and Gram-Positive Bacteria of Hydrothermal Carbon Nanoparticles Associated with Bac8c^2,5Leu Antimicrobial Peptide

ACS Omega. 2022 May 5;7(19):16402-16413. doi: 10.1021/acsomega.2c00305. eCollection 2022 May 17.

Authors

Affiliations

¹ National Institute of Metrological Research (INRiM), 10135 Torino, Italy.
² Department of Electronics and Telecommunications, Politecnico di Torino, 10129 Torino, Italy.
³ Department of Chemistry, University of Torino, 10125 Torino, Italy.
⁴ Department of Chemistry, Royal College of Surgeons in Ireland (RCSI), Dublin 2, Ireland.

Abstract

Antimicrobial peptides (AMPs) are widely studied as therapeutic agents due to their broad-spectrum efficacy against infections. However, their clinical use is hampered by the low in vivo bioavailability and systemic toxicity. Such limitations might be overcome by using appropriate drug delivery systems. Here, the preparation of a drug delivery system (DDS) by physical conjugation of an arginine-rich peptide and hydrothermal carbon nanoparticles (CNPs) has been explored, and its antimicrobial efficacy against Eschericia coli (E. coli) and Staphylococcus aureus investigated in comparison with the unloaded carrier and the free peptide. The mechanism of interaction between CNPs and the bacteria was investigated by scanning electron microscopy and a combined dielectrophoresis-Raman spectroscopy method for real-time analysis. In view of a possible systemic administration, the effect of proteins on the stability of the DDS was investigated by using albumin as a model protein. The peptide was bounded electrostatically to the CNPs surface, establishing an equilibrium modulated by pH and albumin. The DDS exhibited antimicrobial activity toward the two bacterial strains, albeit lower as compared to the free peptide. The decrease in effectiveness toward E. coli was likely due to the rapid formation of a particle-induced extracellular matrix. The present results are relevant for the future development of hydrothermal CNPs as drug delivery agents of AMPs.