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Co-delivery of doxorubicin and RNA using pH-sensitive poly (β-amino ester) nanoparticles for reversal of multidrug resistance of breast cancer

Paper ID Volume ID Publish Year Pages File Format Full-Text
6025 454 2014 13 PDF Available
Title
Co-delivery of doxorubicin and RNA using pH-sensitive poly (β-amino ester) nanoparticles for reversal of multidrug resistance of breast cancer
Abstract

An appropriate co-delivery system for chemotherapeutic agents and nucleic acid drugs will provide a more efficacious approach for the treatment of breast cancer by reversing multidrug resistance (MDR). In this work, a new amphiphilic poly (β-amino ester), poly[(1,4-butanediol)-diacrylate-β-5-polyethylenimine]-block-poly[(1,4-butanediol)-diacrylate-β-5-hydroxy amylamine] (PDP-PDHA) was synthesized, and the doxorubicin (DOX) and survivin-targeting shRNA (shSur) co-loading nanoparticle (PDNs) were prepared. The pH-sensitive poly[(1,4-butanediol) diacrylate-β-5-hydroxy amylamine] (PDHA) endowed PDNs both pH-triggered drug release characteristics and enhanced endo/lysosomal escape ability, thus improving the cytotoxicity of DOX and the transfection efficiency. PDNs also increased the DOX accumulation, down-regulated 57.7% survivin expression, induced 80.8% cell apoptosis and changed the cell cycle in MCF-7/ADR cells. In the MCF-7/ADR tumor-bearing mice models, after administrated intravenously, PDNs raised the accumulation of DOX and shSur in the tumor tissue by 10.4 and 20.2 folds, respectively, resulting in obvious inhibition of the tumor growth with tumor inhibiting rate of 95.9%. The combination of DOX and RNA interference showed synergistic effect on overcoming MDR. Therefore, PDNs could be a promising co-delivery vector for effective therapy of drug resistant breast cancer.

Keywords
Co-delivery; Doxorubicin; Multidrug resistance; pH-sensitive; Poly (β-amino ester); RNA interference
First Page Preview
Co-delivery of doxorubicin and RNA using pH-sensitive poly (β-amino ester) nanoparticles for reversal of multidrug resistance of breast cancer
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 35, Issue 23, July 2014, Pages 6047–6059
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering