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Dual subcellular compartment delivery of doxorubicin to overcome drug resistant and enhance antitumor activity.
Song, Yan-feng; Liu, Dao-zhou; Cheng, Ying; Liu, Miao; Ye, Wei-liang; Zhang, Bang-le; Liu, Xin-you; Zhou, Si-yuan.
Afiliación
  • Song YF; Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
  • Liu DZ; Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
  • Cheng Y; Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
  • Liu M; Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
  • Ye WL; Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
  • Zhang BL; Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
  • Liu XY; Department of Pharmacy, Tangtu Hospital, Fourth Military Medical University, Xi'an 710032, China.
  • Zhou SY; Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
Sci Rep ; 5: 16125, 2015 Nov 04.
Article en En | MEDLINE | ID: mdl-26530454
In order to overcome drug resistant and enhance antitumor activity of DOX, a new pH-sensitive micelle (DOX/DQA-DOX@DSPE-hyd-PEG-AA) was prepared to simultaneously deliver DOX to nucleus and mitochondria. Drug released from DOX/DQA-DOX@DSPE-hyd-PEG-AA showed a pH-dependent manner. DOX/DQA-DOX@DSPE-hyd-PEG-AA induced the depolarization of mitochondria and apoptosis in MDA-MB-231/ADR cells and A549 cells, which resulted in the high cytotoxicity of DOX/DQA-DOX@DSPE-hyd-PEG-AA against MDA-MB-231/ADR cells and A549 cells. Confocal microscopy confirmed that DOX/DQA-DOX@DSPE-hyd-PEG-AA simultaneously delivered DQA-DOX and DOX to the mitochondria and nucleus of tumor cell. After DOX/DQA-DOX@DSPE-hyd-PEG-AA was injected to the tumor-bearing nude mice by the tail vein, DOX was mainly found in tumor tissue. But DOX was widely distributed in the whole body after the administration of free DOX. Compared with free DOX, the same dose of DOX/DQA-DOX@DSPE-hyd-PEG-AA significantly inhibited the growth of DOX-resistant tumor in tumor-bearing mice without obvious systemic toxicity. Therefore, dual subcellular compartment delivery of DOX greatly enhanced the antitumor activity of DOX on DOX-resistant tumor. DOX/DQA-DOX@DSPE-hyd-PEG-AA has the potential in target therapy for DOX-resistant tumor.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Portadores de Fármacos / Doxorrubicina / Apoptosis / Antibióticos Antineoplásicos Límite: Animals / Female / Humans Idioma: En Revista: Sci Rep Año: 2015 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Portadores de Fármacos / Doxorrubicina / Apoptosis / Antibióticos Antineoplásicos Límite: Animals / Female / Humans Idioma: En Revista: Sci Rep Año: 2015 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido