期刊
NANOMEDICINE
卷 7, 期 1, 页码 65-78出版社
FUTURE MEDICINE LTD
DOI: 10.2217/NNM.11.93
关键词
MCF-7 breast cancer cell; micelle-like nanoparticle; multidrug resistance; P-glycoprotein; polyethylenimine; siRNA delivery
资金
- Department of Education of the Navarra Regional Government (Spain)
- NHI [RO1CA121838, 1U54CA151881]
Aims: Multidrug resistance (MDR) mediated by overexpression of drug efflux transporters such as P-glycoprotein (P-gp), is a major problem, limiting successful chemotherapy of breast cancer. The use of siRNA to inhibit P-gp expression in MDR tumors is an attractive strategy to improve the effectiveness of anticancer drugs. Method: We have synthesized a novel conjugate between a phospholipid (dioleoylphosphatidylethanolamine) and polyethylenimine (PEI) for siRNA delivery, for the purpose of silencing P-gp to overcome doxorubicin resistance in MCF-7 human breast cancer cells. Results: The dioleoylphosphatidylethanolamine-PEI conjugate enhanced the transfection efficacy of low-molecularweight PEI, which was otherwise totally ineffective. In addition, the polyethylene glycol/lipid coating of the new complexes gave rise to small micelle-like nanoparticles with improved biocompatibility properties. Both coated and noncoated formulations delivered P-gp-specific siRNA to MDR cells. Discussion: The combination of doxorubicin and P-gp silencing formulations led to a twofold increase of doxorubicin uptake and a significant improvement of the therapeutic effect of doxorubicin in resistant cells.
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