Gold nanoparticles enhance the effect of tyrosine kinase inhibitors in acute myeloid leukemia therapy.
Int J Nanomedicine
; 11: 641-60, 2016.
Article
em En
| MEDLINE
| ID: mdl-26929621
BACKGROUND AND AIMS: Every year, in Europe, acute myeloid leukemia (AML) is diagnosed in thousands of adults. For most subtypes of AML, the backbone of treatment was introduced nearly 40 years ago as a combination of cytosine arabinoside with an anthracycline. This therapy is still the worldwide standard of care. Two-thirds of patients achieve complete remission, although most of them ultimately relapse. Since the FLT3 mutation is the most frequent, it serves as a key molecular target for tyrosine kinase inhibitors (TKIs) that inhibit FLT3 kinase. In this study, we report the conjugation of TKIs onto spherical gold nanoparticles. MATERIALS AND METHODS: The internalization of TKI-nanocarriers was proved by the strongly scattered light from gold nanoparticles and was correlated with the results obtained by transmission electron microscopy and dark-field microscopy. The therapeutic effect of the newly designed drugs was investigated by several methods including cell counting assay as well as the MTT assay. RESULTS: We report the newly described bioconjugates to be superior when compared with the drug alone, with data confirmed by state-of-the-art analyses of internalization, cell biology, gene analysis for FLT3-IDT gene, and Western blotting to assess degradation of the FLT3 protein. CONCLUSION: The effective transmembrane delivery and increased efficacy validate its use as a potential therapeutic.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Portadores de Fármacos
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Leucemia Mieloide Aguda
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Sistemas de Liberação de Medicamentos
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Inibidores de Proteínas Quinases
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Nanopartículas Metálicas
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Ouro
Limite:
Humans
Idioma:
En
Revista:
Int J Nanomedicine
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Romênia
País de publicação:
Nova Zelândia