Research

Imaging Local Drug Delivery

Even though orthopaedic surgeons take great care to avoid infections, a substantial number of patients develop infections subsequent to arthroplasty. The standard of care to resolve these infections is a two-stage revision; however, these procedures fail approximately 10% of the time due to the antimicrobial not penetrating into all infected tissue at a sufficient concentration and adequate duration. To increase success rates, clinicians need a reliable way to measure the concentration of antimicrobial delivered to tissue surrounding the implant to allow the clinician to perform quality control on his/her technical performance and to ensure that therapeutic levels are met throughout the tissue where microbes are likely to reside. To address this problem, we are developing techniques to image the concentration of antimicrobial that has been delivered to tissue with sufficient spatial and temporal resolution.

Drug Targeting to Cancer

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A novel approach to treat cancer more selectively is achieved by targeting drugs to cells via conjugating the drug or imaging agent to an antibody or ligand for a cell surface receptor that is over-expressed by the target cell population. Caplan’s lab has developed biophysical models showing that enhanced specificity can be obtained by multivalency of binding moieties. The lab has also investigated the binding specificity of a multivalent construct and shown that specificity of approximately 10-to-1 (cancer to non-cancer) can be achieved.

 

 

 

 

 

 

 

 

 

Tentacle Probes (Multivalent DNA Probes)

False-positive results are a common problem in real-time PCR identification of DNA sequences that differ from near neighbors by a single nucleotide polymorphism (SNP) or deletion. Tentacle Probes™, cooperative reagents with both a capture and a detection probe based on specific cell-targeting principles, were developed for Yersinia pestis and Bacillus anthracis detection. Caplan’s lab compared TaqMan-MGB probes to Tentacle Probes for SNP and deletion detection based on the presence or absence of a growth curve. Although the TaqMan-MGB probes frequently resulted in false–positive results when boil preps of environmental samples of near neighbors were tested, Tentacle Probes resulted in no false-positive results. The pictures (left) show a Tentacle Probe remaining in the non-fluorescent stem-loop structure when encountering a false analyte (top) or extending to its fluorescent form when encountering a true analyte.