Multifunctional nanoparticles improve therapeutic effect for breast cancer by simultaneously antagonizing multiple mechanisms of multidrug resistance.

Abstract

For efficient reversal of multidrug resistance (MDR) in chemotherapy for breast cancer, multifunctional self-assembled nanoparticles (MSN) based on a new amphiphilic copolymer consisting of bioreducible poly[bis(2-hydroxylethyl)-disulfide-diacrylate-β-tetraethylenepentamine] and polycaprolactone (PBD-PCL) were constructed and characterized. shRNA targeting the apoptosis-inhibiting gene, Survivin, was incorporated into the nanoparticles with high RNA interference efficiency. PBD-PCL significantly inhibited the activity of P-glycoprotein, one of the most well-described drug-efflux pumps, and glutathione S-transferase, an important detoxification enzyme. MSN achieved colocalization of RNA and doxorubicin in tumors after intravenous administration and showed remarkable antitumor efficacy in MDR tumor-bearing mice with less side-effect than drug combination therapy. This was a new attempt to overcome MDR against three different mechanisms of MDR simutaneously: overexpression of drug efflux protein, activation of detoxification system, and blockage of apoptosis. These results indicated that the PBD-PCL-based MSN had obvious potential for therapy of breast cancer.

• Authors: Qi Yin, Jianan Shen, Zhiwen Zhang, Haijun Yu, Lingli Chen, Wangwen Gu, Yaping Li
• Journal: Biomacromolecules (Biomacromolecules) Vol. 14 Issue 7 Pg. 2242-52 (Jul 08 2013) ISSN: 1526-4602 [Electronic] United States
• PMID: 23682680 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Acrylates
• Apoptosis Regulatory Proteins
• Birc5 protein, mouse
• Drug Carriers
• Inhibitor of Apoptosis Proteins
• Polyesters
• RNA, Small Interfering
• Repressor Proteins
• Survivin
• polycaprolactone
• Doxorubicin
• Glutathione Transferase

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (antagonists & inhibitors)
• Acrylates (chemistry)
• Animals
• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (genetics, metabolism)
• Breast Neoplasms (drug therapy)
• Cell Cycle
• Cell Line, Tumor
• Doxorubicin (therapeutic use)
• Drug Carriers (therapeutic use)
• Drug Resistance, Multiple (drug effects)
• Drug Resistance, Neoplasm (drug effects)
• Female
• Glutathione Transferase (antagonists & inhibitors)
• Humans
• Inhibitor of Apoptosis Proteins (genetics, metabolism)
• MCF-7 Cells
• Male
• Mice
• Mice, Inbred BALB C
• Nanoparticles (therapeutic use)
• Polyesters (chemistry)
• RNA Interference
• RNA, Small Interfering
• Repressor Proteins (genetics, metabolism)
• Survivin