DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS

Noninvasive Thermal Ablation of Osteomyelitis-Causing Bacteria Using Functionalized Nanoparticles

Principal Investigator: NELSON, DANIEL C
Institution Receiving Award: MARYLAND, UNIVERSITY OF, COLLEGE PARK
Program: PRORP
Proposal Number: OR090059
Award Number: W81XWH-10-1-0756
Funding Mechanism: Hypothesis Development Award
Partnering Awards:
Award Amount: $149,799.00


PUBLIC ABSTRACT

Bone infection, also known as osteomyelitis, is a serious complication of traumatic wounds obtained on the battlefield. These infections often contain multiple bacterial pathogens with varying degrees of antibiotic resistance. Our proposal takes a bionanotechnology approach to address these infections that completely bypasses the use of common antibiotics. We aim to target gold nanoshells to the surface of bacteria which can then be heated to kill the bacteria in a process known as thermal ablation. The heating will be accomplished by the use of near infrared (IR) radiation, which otherwise passes harmlessly through the human body. The gold nanoshells are known to instantly heat to high temperatures when exposed to IR radiation. In principle, these temperatures are high enough to thermally ablate any cell in close proximity to the particle. Due to the rapid dissipation of thermal energy over very short distances, it is expected that only cells in direct contact with gold particles will be killed and surrounding cells (i.e. human tissues) will remain unaffected. The key to this proposal is the method we will use to target and deliver the gold nanoshells to the bacterial surface. First, we will engineer a scaffold protein, PlyCB, to contain binding sites that will form tight bonds with the gold nanoshells. Next, we will further engineer PlyCB to display specific bacterial recognition domains that are derived from bacteriophage tail fibers. Using these nanomachines, we will demonstrate selective binding and thermal ablation of osteomyelitis-causing pathogens.