Development of antibody-tagged nanoparticles for detection of transplant rejection using biomagnetic sensors.
Organ transplantation is a life-saving procedure and the preferred method of treatment for a growing number of disease states. The advent of new immunosuppressants and improved care has led to great advances in both patient and graft survival. However, acute T-cell-mediated graft rejection occurs in a significant quantity of recipients and remains a life-threatening condition. Acute rejection is associated with decrease in long-term graft survival, demonstrating a need to carefully monitor transplant patients. Current diagnostic criteria for transplant rejection rely on invasive tissue biopsies or relatively nonspecific clinical features. A noninvasive way is needed to detect, localize, and monitor transplant rejection. Capitalizing on advances in targeted contrast agents and magnetic-based detection technology, we developed anti-CD3 antibody-tagged nanoparticles. T cells were found to bind preferentially to antibody-tagged nanoparticles, as identified through light microscopy, transmission electron microscopy, and confocal microscopy. Using mouse skin graft models, we were also able to demonstrate in vivo vascular delivery of T-cell targeted nanoparticles. We conclude that targeting lymphocytes with magnetic nanoparticles is conducive to developing a novel, noninvasive strategy for identifying transplant rejection.
Department of Pathology, University of New Mexico, and Cancer Research and Treatment Center, Albuquerque, NM, USA.
Kimberly S
KS
Butler
Debbie M
DM
Lovato
Natalie L
NL
Adolphi
Robert
R
Belfon
Danielle L
DL
Fegan
Todd C
TC
Monson
Helen J
HJ
Hathaway
Dale L
DL
Huber
T E
TE
Tessier
H C
HC
Bryant
Edward R
ER
Flynn
Richard S
RS
Larson
D000818:Animals; D000906:Antibodies / Q000737:chemistry* / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D006084:Graft Rejection / Q000175:diagnosis* / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D019169:Jurkat Cells; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D060306:Magnetometry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D012867:Skin / Q000473:pathology; D016038:Skin Transplantation; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D000906:Antibodies; D017252:CD3 Complex; D058185:Magnetite Nanoparticles