Nanoparticle-mediated measurement of target-drug binding in cancer cells.
ACS Nano
; 5(11): 9216-24, 2011 Nov 22.
Article
en En
| MEDLINE
| ID: mdl-21962084
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ftalazinas
/
Piperazinas
/
Técnicas Biosensibles
/
Poli(ADP-Ribosa) Polimerasas
/
Nanotecnología
/
Inhibidores Enzimáticos
/
Nanopartículas
/
Terapia Molecular Dirigida
Tipo de estudio:
Guideline
/
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
ACS Nano
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos