TARGETED NANOPARTICLE THERAPY FOR OSTEOMYELITIS

Abstract

Staphylococcus aureus is the most frequent pathogen associated with osteomyelitis, a localized bone infection, which results in gradual bone loss. Intracellular survival, antibiotic resistance, and the ability of S. aureus to evade host immune response result in a recurrent and persistent infection, which present significant challenges in treating osteomyelitis. Extreme cases of osteomyelitis may lead to amputation of the affected limbs. Metal-based antimicrobial nanoparticles are easier to develop and show efficacy against a wide range of bacterial species. Silver (Ag) and Copper (Cu) metallic nanoparticles exhibit potent antimicrobial activity due to the release of lethal metallic ions and formation of reactive oxygen species. The metallic nanoparticles may also induce organ and systemic toxicity in humans. Specific S. aureus components or overexpressed tissue biomarkers in bone infections could be targeted to deliver active therapeutics, thereby reducing drug dosage and systemic toxicity. This study aimed to develop silver-copper based antibacterial nanoparticles that can be conjugated to specific biomolecules to target the site of infection. Boron-doped silver-copper (AgCuB) alloy nanoparticles exhibited the highest antibacterial activity among the synthesized nanoparticles. Three types of biomolecules were conjugated to boron-doped silver-copper (AgCuB), namely anti-osteoblast cadherin antibody (osteoblast targeting), ubiquicidin (bacteria targeting), and CD154 (infected osteoblast targeting). The conjugated AgCuB nanoparticles effectively gained access to the infected osteoblasts than non-conjugated nanoparticles and were effective against intracellular S. aureus. The targeting AgCuB nanoparticles could prove beneficial as an alternative therapy for treating S. aureus associated osteomyelitis.

Date of Award	2020
Original language	American English
Awarding Institution	HBKU College of Health & Life Sciences