(387c) Award Submission: The Binary Effect on Drug-Resistant Bacteria of Polymeric Vesicles Appended By Proline-Rich Amino Acid Sequences and Inorganic Nanoparticles

Prevalent research underscores efforts to engineer highly sophisticated nano-vesicles 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 S. aureus infections post-operatively. Technical challenges associated with this aim require a thorough assessment of the chemical properties of synthesis materials and methods. Here, formulations were incorporated into polymeric, biocompatible vesicles called polymersomes that self-assemble via hydrophobicity interactions of admixed aqueous and organic substances. Nano-polymersomes were synthesized using a high molecular weight amphiphilic block copolymer, and were conjugated to include antimicrobial peptides (AMPs) along the peripheral hydrophilic region and silver (Ag) nanoparticles inside their hydrophobic corona. In vitro testing on bacterial and human cell lines indicated that finely tuned treatment concentrations of AMP and Ag nanoparticles in polymersomes synergistically inhibited the growth of MRSA without posing significant side effects, as compared with other potent treatment strategies. In particular, a ratio of silver-to-AMP of about 1:1.9, corresponding to approximately 0.1 mg/ml of silver nanoparticles and 40 μM of the peptide, yielded complete MRSA inhibition over a 23-hour time frame. The silver nanoparticles generate bacterial cell wall indentations that prompt the influx of external entities and the outflow of vital proteins or nutrients. This weakening of lipopolysaccharide permeability barriers promotes the unimpeded cellular translocation of contiguous AMP molecules, which can then disrupt internal processes including DNA or protein synthesis. This bacteriostatic activity, coupled with nominal cytotoxicity towards native human dermal fibroblast cells, extends the potential for AMP/Ag nanoparticle polymersome therapies to replace antibiotics in the clinical setting. This study will facilitate contemporary research that is feasible, important, and highly relevant, and possesses the potential to advance knowledge in several fields, including drug delivery, nanotechnology, and artificial immunity.