The Binary Effect on Methicillin-Resistant Staphylococcus aureus of Polymeric Nanovesicles Appended by Proline-Rich Amino Acid Sequences and Inorganic Nanoparticles.

Abstract

Prevalent research underscores efforts to engineer highly sophisticated nanovesicles that are functionalized to combat antibiotic-resistant bacterial infections, especially those caused by methicillin-resistant Staphylococcus aureus (MRSA), and that aid with wound healing or immunomodulation. This is especially relevant for patients who are susceptible to Staphylococcus aureus infections postoperatively. Here, antibacterial formulations are incorporated into polymeric, biocompatible vesicles called polymersomes (PsNPs) that self-assemble via hydrophobic interactions of admixed aqueous and organic substances. Nano-PsNPs are synthesized using a high molecular weight amphiphilic block copolymer, and are conjugated to include antimicrobial peptides (AMPs) along the peripheral hydrophilic region and silver nanoparticles (AgNPs) inside their hydrophobic corona. In vitro testing on bacterial and human cell lines indicates that finely tuned treatment concentrations of AMP and AgNPs in PsNPs synergistically inhibits the growth of MRSA without posing significant side effects, as compared with other potent treatment strategies. A ratio of silver-to-AMP of about 1:5.8 corresponding to ≈11.6 µg mL-1 of silver nanoparticles and 14.3 × 10-6 m of the peptide, yields complete MRSA inhibition over a 23 h time frame. This bacteriostatic activity, coupled with nominal cytotoxicity toward native human dermal fibroblast cells, extends the potential for AMP/AgNP polymersome therapies to replace antibiotics in the clinical setting.