期刊
BIOMACROMOLECULES
卷 14, 期 7, 页码 2242-2252出版社
AMER CHEMICAL SOC
DOI: 10.1021/bm400378x
关键词
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资金
- National Basic Research Program of China [2010CB934000, 2012CB932502, 2013CB932503]
- National Natural Science Foundation of China [30925041, 81230029]
- Shanghai Program [11 nm0505900]
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 bioreducibie Poly[bis(2-hydroxylethyl)-disulfide-diacrylate-beta-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.
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