Metabolism targeting therapy of dichloroacetate-loaded electrospun mats on colorectal cancer.
Drug Deliv
; 22(1): 136-43, 2015 Jan.
Article
em En
| MEDLINE
| ID: mdl-24359441
ABSTRACT
Differences in energy metabolism between tumor cells and normal cells offer an attractive avenue of research into drug targets for tumor therapy. The use of a metabolic modulator (sodium dichloroacetate, DCA), administered in situ, to reverse the "Warburg effect" of tumor cells has been demonstrated as an effective tumor therapy. Herein, DCA and diisopropylamine dichloroacetate (DADA) were incorporated separately into polylactide (PLA) electrospun mats and applied to C26 tumor-bearing mice via in situ administration. After 12 d of treatment, the tumor suppression rates of 75% and 84% were achieved in the DC group (treated with a DCA-loaded mat) and the DA group (treated with a DADA-loaded mat), respectively. With tolerable physiologic toxicity under high local concentration, the DA group showed a 95% tumor suppression rate without any recurrence after 15 d of therapy. The desirable therapeutic effects of these metabolic modulators should ascribe to the energy-central metabolism-targeting effects of DCA and DADA, which were demonstrated both in vitro and in vivo. Therefore, DCA- and DADA-loaded mats are the effective anti-cancer drugs dosages to discriminate between tumor cells and normal cells for minimizing systemic toxicity.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Poliésteres
/
Neoplasias Colorretais
/
Ácido Dicloroacético
/
Compostos de Amônio Quaternário
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article