EpCAM aptamer mediated cancer cell specific delivery of EpCAM siRNA using polymeric nanocomplex
Authors: Narayanan Janakiraman
Vikas Khetan
Subramanian Krishnakumar
Sailaja Eluchuri
Nithya Subramanian
Prasanna Kumar Athalya
Rupinder K Kanwar
Jagat R Kanwar
Journal: Journal of Biomedical Science (2015)
Discipline: CLINICAL MEDICINE
Keywords: Epithelial cell adhesion molecule; EpCAM; aptamer; siRNA; cancer cells
Affiliations: Department of Nanobiotechnology, Vision Research Foundation, Kamalnayan Bajaj Institute for Research in Vision and Ophthalmology, 18 College Road, Chennai, 600006, Tamil Nadu, India. ., Nanomedicine Laboratory of Immunology and Molecular Biomedical Research (LIMBR), School of Medicine (SoM), Molecular and Medical Research (MMR) Strategic Research Centre, Faculty of Health, Deakin University, Geelong, Victoria, 3217, Australia. ., Departments of Ocular Oncology and Vitreoretina, Medical Research Foundation, Sankara Nethralaya, Chennai, India. ., L & T Ocular Pathology department, Vision Research Foundation, Kamalnayan Bajaj Institute for Research in Vision and Ophthalmology, Chennai, India. .

Abstract:  Background: Epithelial cell adhesion molecule (EpCAM) is overexpressed in solid tumors and regarded as a putative cancer stem cell marker. Here, we report that employing EpCAM aptamer (EpApt) and EpCAM siRNA (SiEp) dual approach, for the targeted delivery of siRNA to EpCAM positive cancer cells, efficiently inhibits cancer cell proliferation. Results: Targeted delivery of siRNA using polyethyleneimine is one of the efficient methods for gene delivery, and thus, we developed a novel aptamer-PEI-siRNA nanocomplex for EpCAM targeting. PEI nanocomplex synthesized with EpCAM aptamer (EpApt) and EpCAM siRNA (SiEp) showed 198 nm diameter sized particles by dynamic light scattering, spherical shaped particles, of 151 ¬± 11 nm size by TEM. The surface charge of the nanoparticles was -30.0 mV using zeta potential measurements. Gel retardation assay confirmed the PEI-EpApt-SiEp nanoparticles formation. The difference in size observed by DLS and TEM could be due to coating of aptamer and siRNA on PEI nanocore. Flow cytometry analysis revealed that PEI-EpApt-SiEp has superior binding to cancer cells compared to EpApt or scramble aptamer (ScrApt) or PEI-ScrApt-SiEp. PEI-EpApt-SiEp downregulated EpCAM and inhibited selectively the cell proliferation of MCF-7 and WERI-Rb1 cells. Conclusions: The PEI nanocomplex fabricated with EpApt and siEp was able to target EpCAM tumor cells, deliver the siRNA and silence the target gene. This nanocomplex exhibited decreased cell proliferation than the scrambled aptamer loaded nanocomplex in the EpCAM expressing cancer cells and may have potential for EpCAM targeting in vivo. 

Retracted: No

PubPeer comments:
 There is an instance of image duplication in this paper. The EpApt alone and ScrApt alone panels of Figure 4 have been duplicated. This is shown in the attached figure - see blue boxes in the top row of the phase contrast image.  , 
 We are grateful for informing us on the error. we apologise and we have informed the journal and we are working to submit an erratum , 
 There is already an Editor s note in the journal site stating  Change history 17 July 2020 Editoru2019s Note: The Editor-in-Chief is currently investigating this article as concerns have been raised about the integrity of the data reported in this article. Further editorial action may be taken as appropriate once the investigation into the concerns is complete and all parties have been given an opportunity to respond in full. Here is that link: https: jbiomedsci.biomedcentral.com articles 10.1186 s12929-014-0108-9#change-history , 
 Correction published [8 November 2020] .  After published the article [1] the author became aware of a mistake in the Fig. 4 (upper panel section C). Due to an error that occurred inadvertently at the time of figure assembly, an incorrect image for ScrApt alone sample was included. The correct version of the Fig. 4 is given below. This change does not affect the conclusions and interpretations of the article in any way. The authors sincerely apologize for this unintentional error.  ,