Label-free imaging of drug distribution and metabolism in colon cancer cells by Raman microscopy.
Analyst
; 139(5): 1155-61, 2014 Mar 07.
Article
em En
| MEDLINE
| ID: mdl-24427772
ABSTRACT
Targeted cancer therapies block cancer growth and spread using small molecules. Many molecular targets for an epidermal growth factor receptor (EGFR) selectively compete with the adenosine triphosphate-binding site of its tyrosine kinase domain. Detection of molecular targeted agents and their metabolites in cells/tissues by label-free imaging is attractive because dyes or fluorescent labels may be toxic or invasive. Here, label-free Raman microscopy is applied to show the spatial distribution of the molecular targeted drug erlotinib within the cell. The Raman images show that the drug is clustered at the EGFR protein at the membrane and induces receptor internalization. The changes within the Raman spectrum of erlotinib measured in cells as compared to the free-erlotinib spectrum indicate that erlotinib is metabolized within cells to its demethylated derivative. This study provides detailed insights into the drug targeting mechanism at the atomic level in cells. It demonstrates that Raman microscopy will open avenues as a non-invasive and label-free technique to investigate pharmacokinetics at the highest possible resolution in living cells.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Quinazolinas
/
Análise Espectral Raman
/
Neoplasias do Colo
Limite:
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article