Nanoparticle-Mediated Measurement of Target–Drug Binding in Cancer Cells
| Autor: | Hakho Lee, Ralph Weissleder, David Issadore, Thomas Reiner, Changwook Min, Katherine S. Yang, Rostic Gorbatov, Adeeti Ullal |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Drug
Time Factors Materials science Cell Survival Point-of-Care Systems media_common.quotation_subject General Physics and Astronomy Biosensing Techniques Poly(ADP-ribose) Polymerase Inhibitors Poly (ADP-Ribose) Polymerase Inhibitor Article Piperazines Cell Line Tumor Humans Nanotechnology General Materials Science Molecular Targeted Therapy Enzyme Inhibitors Polymerase media_common biology General Engineering Biochemistry Cell culture Drug delivery Cancer cell biology.protein Biophysics Nanoparticles Phthalazines Target protein Poly(ADP-ribose) Polymerases Ex vivo |
| Zdroj: | ACS Nano. 5:9216-9224 |
| ISSN: | 1936-086X 1936-0851 |
| Popis: | Responses to molecularly targeted therapies can be highly variable and depend on mutations, fluctuations in target protein levels in individual cells, and drug delivery. The ability to rapidly quantitate drug response in cells harvested from patients in a point-of-care setting would have far reaching implications. Capitalizing on recent developments with miniaturized NMR technologies, we have developed a magnetic nanoparticle-based approach to directly measure both target expression and drug binding in scant human cells. The method involves covalent conjugation of the small-molecule drug to a magnetic nanoparticle that is then used as a read-out for target expression and drug-binding affinity. Using poly(ADP-ribose) polymerase (PARP) inhibition as a model system, we developed an approach to distinguish differential expression of PARP in scant cells with excellent correlation to gold standards, the ability to mimic drug pharmacodynamics ex vivo through competitive target-drug binding, and the potential to perform such measurements in clinical samples. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|