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Azoreductase-Responsive Metal-Organic Framework-Based Nanodrug for Enhanced Cancer Therapy via Breaking Hypoxia-induced Chemoresistance.
Huang, Caixia; Tan, Wenlong; Zheng, Jing; Zhu, Cong; Huo, Jia; Yang, Ronghua.
Afiliación
  • Huang C; State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering , Hunan University , Changsha 410082 , China.
  • Tan W; State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering , Hunan University , Changsha 410082 , China.
  • Zheng J; State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering , Hunan University , Changsha 410082 , China.
  • Zhu C; State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering , Hunan University , Changsha 410082 , China.
  • Huo J; State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering , Hunan University , Changsha 410082 , China.
  • Yang R; Shenzhen Research Institute , Hunan University , Shenzhen 518000 , Guangdong , China.
ACS Appl Mater Interfaces ; 11(29): 25740-25749, 2019 Jul 24.
Article en En | MEDLINE | ID: mdl-31251022
The insufficient oxygen supply may cause hypoxia in a solid tumor, which can lead to drug resistance and unsatisfactory chemotherapy effect. To address this issue, a new nanodrug has been developed with azoreductase-responsive functional metal-organic frameworks (AMOFs), where chemotherapeutic drugs were encapsulated in the AMOFs and small interfering RNAs (siRNAs) were absorbed on the surface of AMOFs. The siRNA was designed to contain hypoxia-inducible factor (HIF)-1α against RX-0047, which can induce significant downregulation of HIF-1α protein. The azobenzene units within the frameworks of AMOFs could be reduced to amines by the highly expressed azoreductase under the oxygen-deficient environment, which results in azoreductase-responsive release of the encapsulated drugs and siRNAs under the hypoxic condition. Therefore, once the drug-loaded AMOF entered the hypoxic cancer cells, the azoreductase-responsive release of siRNA could decrease the efflux of chemotherapeutic drugs via inhibiting the expressions of HIF-1α, multidrug resistance gene 1, and P-glycoprotein. This nanodrug can thus efficiently break hypoxia-induced chemoresistance and result in high-efficient cancer therapy in hypoxic tumors. As far as we know, this is the first attempt to construct an AMOF-based nanodrug with hypoxic harvesting behaviors. This proof-of-concept research provides a simple strategy for the construction of hypoxic-responsive AMOFs and also offers a unique on-command drug delivery platform, which can effectively break hypoxia-induced chemoresistance.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oligonucleótidos / Portadores de Fármacos / Resistencia a Antineoplásicos / Nanoestructuras / NADH NADPH Oxidorreductasas / Proteínas de Neoplasias / Neoplasias Experimentales Tipo de estudio: Prognostic_studies Idioma: En Revista: ACS Appl Mater Interfaces Asunto de la revista: BIOTECNOLOGIA / ENGENHARIA BIOMEDICA Año: 2019 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oligonucleótidos / Portadores de Fármacos / Resistencia a Antineoplásicos / Nanoestructuras / NADH NADPH Oxidorreductasas / Proteínas de Neoplasias / Neoplasias Experimentales Tipo de estudio: Prognostic_studies Idioma: En Revista: ACS Appl Mater Interfaces Asunto de la revista: BIOTECNOLOGIA / ENGENHARIA BIOMEDICA Año: 2019 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos