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.
journal_name
Biomacromoleculesjournal_title
Biomacromoleculesauthors
Yin Q,Shen J,Zhang Z,Yu H,Chen L,Gu W,Li Ydoi
10.1021/bm400378xsubject
Has Abstractpub_date
2013-07-08 00:00:00pages
2242-52issue
7eissn
1525-7797issn
1526-4602journal_volume
14pub_type
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