Developing Protein-Antitumoral Drug Nanoconjugates as Bifunctional Antimicrobial Agents.

Abstract

A novel concept about bifunctional antimicrobial drugs, based on self-assembling protein nanoparticles, has been evaluated here over two biofilm-forming pathogens, namely Pseudomonas aeruginosa and Staphylococcus aureus. Two structurally different antimicrobial peptides (GWH1 and PaDBS1R1) were engineered to form regular nanoparticles of around 35 nm, to which the small molecular weight drug Floxuridine was covalently conjugated. Both the assembled peptides and the chemical, a conventional cytotoxic drug used in oncotherapy, showed potent antimicrobial activities that were enhanced by the combination of both molecules in single pharmacological entities. Therefore, the resulting prototypes show promises as innovative nanomedicines, being potential alternatives to conventional antibiotics. The biological performance and easy fabrication of these materials fully support the design of protein-based hybrid constructs for combined molecular therapies, expected to have broad applicability beyond antimicrobial medicines. In addition, the approach taken here validates the functional exploration and repurposing of antitumoral drugs, which at low concentrations perform well as unexpected biofilm-inhibiting agents.