Target-specific delivery of doxorubicin to retinoblastoma using epithelial cell adhesion molecule aptamer

Subramanian, Nithya, Raghunathan, Vaishnavi, Kanwar, Jagat R., Kanwar, Rupinder K., Elchuri, Sailaja V., Khetan, Vikas and Krishnakumar, Subramanian 2012, Target-specific delivery of doxorubicin to retinoblastoma using epithelial cell adhesion molecule aptamer, Molecular vision, vol. 18, pp. 2783-2795.

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Title Target-specific delivery of doxorubicin to retinoblastoma using epithelial cell adhesion molecule aptamer
Author(s) Subramanian, Nithya
Raghunathan, Vaishnavi
Kanwar, Jagat R.ORCID iD for Kanwar, Jagat R.
Kanwar, Rupinder K.
Elchuri, Sailaja V.
Khetan, Vikas
Krishnakumar, Subramanian
Journal name Molecular vision
Volume number 18
Start page 2783
End page 2795
Total pages 13
Publisher Molecular Vision
Place of publication Atlanta, Ga.
Publication date 2012
ISSN 1090-0535
Summary PURPOSE: To study target-specific delivery of doxorubicin (Dox) using an RNA aptamer against epithelial cell adhesion molecule (EpCAM) in retinoblastoma (RB) cells. METHODS: The binding affinity of the EpCAM aptamer to RB primary tumor cells, Y79 and WERI-Rb1 cells, and Müller glial cell lines were evaluated with flow cytometry. Formation of physical conjugates of aptamer and Dox was monitored with spectrofluorimetry. Cellular uptake of aptamer-Dox conjugates was monitored through fluorescent microscopy. Drug efficacy was monitored with cell proliferation assay. RESULTS: The EpCAM aptamer (EpDT3) but not the scrambled aptamer (Scr-EpDT3) bound to RB tumor cells, the Y79 and WERI-Rb1 cells. However, the EpCAM aptamer and the scrambled aptamer did not bind to the noncancerous Müller glial cells. The chimeric EpCAM aptamer Dox conjugate (EpDT3-Dox) and the scrambled aptamer Dox conjugate (Scr-EpDT3-Dox) were synthesized and tested on the Y79, WERI-Rb1, and Müller glial cells. The targeted uptake of the EpDT3-Dox aptamer caused cytotoxicity in the Y79 and WERI-Rb1 cells but not in the Müller glial cells. There was no significant binding or consequent cytotoxicity by the Scr-EpDT3-Dox in either cell line. The EpCAM aptamer alone did not cause cytotoxicity in either cell line. CONCLUSIONS: The results show that the EpCAM aptamer-Dox conjugate can selectively deliver the drug to the RB cells there by inhibiting cellular proliferation and not to the noncancerous Müller glial cells. As EpCAM is a cancer stem cell marker, this aptamer-based targeted drug delivery will prevent the undesired effects of non-specific drug activity and will kill cancer stem cells precisely in RB.
Language eng
Field of Research 109999 Technology not elsewhere classified
Socio Economic Objective 970110 Expanding Knowledge in Technology
HERDC Research category C1 Refereed article in a scholarly journal
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Document type: Journal Article
Collection: Centre for Biotechnology and Interdisciplinary Sciences (BioDeakin)
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