Jump to main content
Jump to site search

Issue 13, 2015
Previous Article Next Article

A reduction-dissociable PEG-b-PGAH-b-PEI triblock copolymer as a vehicle for targeted co-delivery of doxorubicin and P-gp siRNA

Author affiliations

Abstract

To enhance the therapeutic efficacy of doxorubicin (DOX) to breast cancer cells, a multifunctional triblock copolymer, poly(ethylene glycol)-block-poly(L-glutamic acid γ-hydrazide)-block-polyethylenimine (PEG-b-PGAH-b-PEI) having a cleavable disulfide linkage between blocks, was developed as a vehicle for targeted co-delivery of DOX and P-glycoprotein (P-gp) siRNA into MCF-7/ADR cells. The PGAH blocks were used to chemically conjugate DOX molecules via hydrazone bonds, while the PEI blocks could complex siRNA through electrostatic interactions. A tumor-targeting agent, folic acid (FA), was attached to the distal ends of the PEG blocks to specifically bind to the folate receptors overexpressed in MCF-7/ADR cells. The DOX-conjugated copolymer would self-assemble in aqueous solutions into cationic nanomicelles, which could condense siRNA to form nanomicelleplexes with an average particle size of ∼194 nm and a positive zeta potential of >+10 mV. The nanomicelleplexes exhibited sustained drug release profiles, and the release rates of DOX and siRNA from the nanomicelleplexes in a reductive acidic environment (pH 5.0 + 10 mM glutathione) were much faster than those under physiological conditions (pH 7.4). FA-decorated nanomicelleplexes were more efficiently internalized by MCF-7/ADR cells via folate-receptor-mediated endocytosis and exhibited a higher cytotoxic effect on MCF-7/ADR cells in comparison with FA-undecorated nanomicelleplexes. Furthermore, the synergistic effects of DOX and P-gp siRNA in inhibiting cell proliferation and inducing apoptosis in MCF-7/ADR cells were achieved by the FA-targeted co-delivery system. The triblock copolymer itself had a low cytotoxicity. These results indicate that the triblock copolymer could serve as an ideal tumor-targeting vehicle for simultaneous delivery of drugs and siRNA in breast cancer therapy.

Graphical abstract: A reduction-dissociable PEG-b-PGAH-b-PEI triblock copolymer as a vehicle for targeted co-delivery of doxorubicin and P-gp siRNA

Back to tab navigation

Publication details

The article was received on 12 Jan 2015, accepted on 26 Jan 2015 and first published on 27 Jan 2015


Article type: Paper
DOI: 10.1039/C5PY00034C
Polym. Chem., 2015,6, 2445-2456

  •   Request permissions

    A reduction-dissociable PEG-b-PGAH-b-PEI triblock copolymer as a vehicle for targeted co-delivery of doxorubicin and P-gp siRNA

    M. Xu, J. Qian, A. Suo, T. Liu, X. Liu and H. Wang, Polym. Chem., 2015, 6, 2445
    DOI: 10.1039/C5PY00034C

Search articles by author

Spotlight

Advertisements