Azoreductase-Responsive Metal-Organic Framework-Based Nanodrug for Enhanced Cancer Therapy via Breaking Hypoxia-induced Chemoresistance.
ACS Appl Mater Interfaces
; 11(29): 25740-25749, 2019 Jul 24.
Article
in En
| MEDLINE
| ID: mdl-31251022
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oligonucleotides
/
Drug Carriers
/
Drug Resistance, Neoplasm
/
Nanostructures
/
NADH, NADPH Oxidoreductases
/
Neoplasm Proteins
/
Neoplasms, Experimental
Type of study:
Prognostic_studies
Language:
En
Journal:
ACS Appl Mater Interfaces
Journal subject:
BIOTECNOLOGIA
/
ENGENHARIA BIOMEDICA
Year:
2019
Document type:
Article
Affiliation country: