A drug-delivery strategy for overcoming drug resistance in breast cancer through targeting of oncofetal fibronectin

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Amajor problem with cancer chemotherapy begins when cells acquire resistance. Drug-resistant cancer cells typically upregulatemulti-drug resistance proteins such as P-glycoprotein (P-gp). However, the lack of overexpressed surface biomarkers has limited the targeted therapy of drug-resistant cancers. Here we report a drug-delivery carrier decoratedwith a targeting ligand for a surface marker protein extra-domain B(EDB) specific to drug-resistant breast cancer cells as a new therapeutic option for the aggressive cancers. We constructed EDB-specific aptide (APT(EDB))-conjugated liposome to simultaneously deliver siRNA(siMDR1) andDox to drug-resistant breast cancer cells. APT(EDB)-LS(Dox, siMDR1) led to enhanced delivery of payloads intoMCF7/ADR cells and showed significantly higher accumulation and retention in the tumors. While either APT(EDB)-LS(Dox) or APT(EDB)-LS(siMDR1) did not lead to appreciable tumor retardation in MCF7/ADR orthotropic model, APT(EDB)-LS(Dox, siMDR1) treatment resulted in significant reduction of the drugresistant breast tumor. Taken together, this study provides a new strategy of drug delivery for drug-resistant cancer therapy. (C)2016 Elsevier Inc. All rights reserved.
Publisher
ELSEVIER SCIENCE BV
Issue Date
2017-02
Language
English
Article Type
Article
Keywords

SMALL INTERFERING RNA; MESOPOROUS SILICA NANOPARTICLES; EXTRA DOMAIN-B; CO-DELIVERY; MULTIDRUG-RESISTANCE; STEM-CELLS; ANTICANCER DRUG; OVARIAN-CANCER; IN-VITRO; SIRNA

Citation

NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE, v.13, no.2, pp.713 - 722

ISSN
1549-9634
DOI
10.1016/j.nano.2016.10.005
URI
http://hdl.handle.net/10203/223308
Appears in Collection
BS-Journal Papers(저널논문)
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