Noninvasive Thermal Ablation of Osteomyelitis-Causing Bacteria using Functionalized Nanoparticles.

摘要

Due to the changing bacteriology and multi-drug resistant nature of osteomyelitis (bone infections) associated with war wounds, choosing appropriate antimicrobial therapy is a challenging task (Calhoun, 2008; Johnaon, 2007; Murray, 2006; Murray, 2008; Yun, 2008). One alternative approach to antibiotics includes the use of near infrared (IR) radiation to thermally kill pathogenic organisms (Kam, 2005; Zharov, 2006). Whereas near IR wavelengths pass harmlessly through the human body, they are known to heat gold nanoshells to high temperatures (>70 C), which in principle will thermally ablate any cell (bacterial or eukaryotic) in close proximity to these particles. Due to the rapid dissipation of thermal energy over very short distances, it is speculated that only cells in direct contact with gold particles will be killed and surrounding tissues will be unaffected (Hu, 2006). The challenge to this approach is to develop a system to bind the gold nanoparticles to the surface of targeted cells. Our aim is to use a scaffold protein, PlyCB, which can be functionalized to bind gold nanoparticles as well as bacterialspecific targeting domains. PlyCB is stable up to 100 C, resistant to proteolysis, high ionic strength, extreme pH conditions, and most detergents, making it a perfect platform for engineering. The top surface of PlyCB will be modified to contain cysteine residues to covalently bind gold nanoparticles (Fig 1). The bottom surface of PlyCB inherently binds streptococcal cells with nanomolar affinity, which will be used for proof-ofprinciple thermal ablation studies. We further propose to engineer the bottom surface to contain an array of binding domains isolated from tail fibers of bacteriophage that are specific for osteomyelitis causing pathogens.