Ag-Cu alloy nanoparticles (NPs) release Ag+ and Cu+ ions which are known to have strong antimicrobial activity, but the toxicity of metallic nanoparticles to host cells undermine their use in the therapeutic applications. This talk will discuss the strategy of forming the Ag-Cu metallic alloy nanoparticles at cold temperature conditions with functional groups on the nanoparticle surface for bio-conjugation to target intracellular infection. Internalized Staphylococcus aureus (S. aureus) bacteria in host cells have developed mechanisms to evade immune response by adopting the phenotype-small colony variant which can persist and survive for longer periods. As a result, the treatment of osteomyelitis due to S. aureus infection has become difficult. Antibiotic treatment against internalized infection may become inefficient due to low penetration of antibiotics, low retention in cells and a high probability of developing antibiotic resistance. Hence our NP treatment strategy which involves the on-site release of ions from the NPs can overcome intracellular infection. In this work, Ag-Cu alloy NPs are targeted to the osteoblast cell membrane via Integrin or Cadherin targeting antibodies. We observed that 4 to 6 hours after targeting, nanoparticles were internalized in the endosomes. The pH of early endosomes and lysosomes is slightly acidic which accelerates the process of ion release from the NPs. Ag+ and Cu+ ions released in the intracellular environment exhibited potent antimicrobial activity where more than 90% of the infection was cleared in 24 hours of incubation and the effectiveness of the particles was tested until 72 hours of incubation. In addition, this method of targeting bone infection minimizes the use of metallic nanoparticles to avoid toxicity to host cells, which may have clinical application for osteomyelitis management and needs to be studied in animal models.

Ag-Cu alloy nanoparticle synthesis and targeting infection in osteoblast cells

2019 Spring National Meeting

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