Synergistically Enhanced Therapeutic Effect of a Carrier-Free HCPT/DOX Nanodrug on Breast Cancer Cells through Improved Cellular Drug Accumulation.
Mol Pharm
; 12(7): 2237-44, 2015 Jul 06.
Article
em En
| MEDLINE
| ID: mdl-25996761
ABSTRACT
We are interested in developing systems for simultaneous delivery of two or more chemotherapeutic agents. Simple physical mixing of drugs may reduce the therapeutic effect and cause unexpected or even dangerous side-effects. For example, when 10-hydroxycamptothecin (HCPT) and doxorubicin (DOX) injection solutions are mixed, the curative effect is actually reduced in clinical practice. In this study we demonstrated that when HCPT and DOX are combined into a single nanoparticle, their toxicity to tumor cells in vitro is synergistically enhanced. We used a simple and "green" reprecipitation method to successfully create a carrier-free dual-drug delivery system by self-nanocrystallization of the drug molecules. When HCPT and DOX were coassembled, they formed small, spherical nanodrug particles with a positive surface charge. Cellular uptake of HCPT was improved and nuclear accumulation increased as much as 1.57-fold in comparison to HCPT alone. The carrier-free HCPT/DOX nanoparticles demonstrated enhanced synergistic cytotoxicity against breast cancer cells in vitro, while an antagonistic effect was observed when HCPT and DOX were directly mixed at high concentration.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Camptotecina
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Portadores de Fármacos
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Doxorrubicina
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Nanopartículas
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Antibióticos Antineoplásicos
Limite:
Female
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Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article