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.

journal_name

Biomacromolecules

journal_title

Biomacromolecules

authors

Yin Q,Shen J,Zhang Z,Yu H,Chen L,Gu W,Li Y

doi

10.1021/bm400378x

subject

Has Abstract

pub_date

2013-07-08 00:00:00

pages

2242-52

issue

7

eissn

1525-7797

issn

1526-4602

journal_volume

14

pub_type

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