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Macromol Biosci. 2017 Apr;17(4). doi: 10.1002/mabi.201600343. Epub 2016 Nov 10.

Multivalent Aptamer-RNA Conjugates for Simple and Efficient Delivery of Doxorubicin/siRNA into Multidrug-Resistant Cells.

Author information

1
Department of Bioscience and Biotechnology, Konkuk University, Seoul, 143-701, Republic of Korea.
2
Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology Zurich (ETHZ), 8093 Zurich, Switzerland.
3
Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, 136-791, Republic of Korea.

Abstract

Multivalent aptamer-siRNA conjugates containing multiple mucin-1 aptamers and BCL2-specific siRNA are synthesized, and doxorubicin, an anthracycline anticancer drug, is loaded into these conjugates through intercalation with nucleic acids. These doxorubicin-incorporated multivalent aptamer-siRNA conjugates are transfected to mucin-1 overexpressing MCF-7 breast cancer cells and their multidrug-resistant cell lines. Doxorubicin-incorporated multivalent aptamer-siRNA conjugates exert promising anticancer effects, such as activation of caspase-3/7 and decrease of cell viability, on multidrug-resistant cancer cells because of their high intracellular uptake efficiency. Thus, this delivery system is an efficient tool for combination oncotherapy with chemotherapeutics and nucleic acid drugs to overcome multidrug resistance.

KEYWORDS:

combination therapy; doxorubicin; multidrug-resistant cancer cells; multivalent aptamers; siRNA

PMID:
27863037
DOI:
10.1002/mabi.201600343
[Indexed for MEDLINE]

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