fulltext.study @t Gmail

Co-delivery of Se nanoparticles and pooled SiRNAs for overcoming drug resistance mediated by P-glycoprotein and class III β-tubulin in drug-resistant breast cancers

Paper ID Volume ID Publish Year Pages File Format Full-Text
144 11 2016 14 PDF Available
Title
Co-delivery of Se nanoparticles and pooled SiRNAs for overcoming drug resistance mediated by P-glycoprotein and class III β-tubulin in drug-resistant breast cancers
Abstract

Drug resistance mediated by P-glycoprotein (P-gp) and class III β-tubulin (β-tubulin III) is a major barrier in microtubule-targeting cancer chemotherapy. In this study, layered double hydroxide nanoparticles (LDHs) were employed to simultaneously deliver selenium (Se) and pooled small interfering RNAs (siRNAs) to achieve therapeutic efficacy. LDH-supported Se nanoparticles (Se@LDH) were compacted with siRNAs (anti-P-gp and anti-β-tubulin III) via electrostatic interactions, which could protect siRNA from degradation. Se@LDH showed excellent abilities to deliver siRNA into cells, including enhancing siRNA internalization, and promoting siRNA escape from endosomes. siRNA transfection experiments further confirmed a higher gene silencing efficiency of Se@LDH than LDH. Interestingly, we found Se@LDH may be a microtubule (MT) stabilizing agent which could inhibit cell proliferation by blocking cell cycle at G2/M phase, disrupting normal mitotic spindle formation and inducing cell apoptosis. When complexed with different specific siRNAs, Se@LDH/siRNA nanoparticles, especially the Se@LDH-pooled siRNAs, exhibit an efficient gene-silencing effect that significantly downregulate the expression of P-gp and β-tubulin III. Moreover, Se@LDH-pooled siRNAs could induce cell apoptosis, change cell morphology and increase cellular ROS levels through change the expression of Bcl-2/Bax, activation of caspase-3, PI3K/AKT/mTOR and MAPK/ERK pathways. These results suggested that co-delivery of Se and pooled siRNAs may be a promising strategy for overcoming the drug resistance mediated by P-gp and β-tubulin III in drug-resistant breast cancers.

Graphical abstractSchematic presentation of Se@LDH-pooled siRNAs synthesis and drug release.Figure optionsDownload full-size imageDownload high-quality image (148 K)Download as PowerPoint slide

Keywords
Selenium; siRNA; Drug resistance; P-glycoprotein; Class III β-tubulin
First Page Preview
Co-delivery of Se nanoparticles and pooled SiRNAs for overcoming drug resistance mediated by P-glycoprotein and class III β-tubulin in drug-resistant breast cancers
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us
Publisher
Database: Elsevier - ScienceDirect
Journal: Acta Biomaterialia - Volume 31, February 2016, Pages 197–210
Authors
, , , , , , , , ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us