EpCAM aptamer mediated cancer cell specific delivery of EpCAM siRNA using polymeric nanocomplex

Journal of Biomedical Science

Subramanian Krishnakumar³  Sailaja Eluchuri¹  Rupinder K Kanwar⁴  Vikas Khetan²  Narayanan Janakiraman¹  Prasanna kumar Athalya⁴  Jagat R Kanwar⁴  Nithya Subramanian⁴ 

[1] Department of Nanobiotechnology, Vision Research Foundation, Kamalnayan Bajaj Institute for Research in Vision and Ophthalmology, 18 College Road, Chennai 600006, Tamil Nadu, India;Departments of Ocular Oncology and Vitreoretina, Medical Research Foundation, Chennai, Sankara Nethralaya, India;L & T Ocular Pathology department, Vision Research Foundation, Kamalnayan Bajaj Institute for Research in Vision and Ophthalmology, Chennai, 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 3217, Victoria, Australia

关键词: Cancer targeting;    siRNA delivery;    PEI-EpApt-SiEp;    Aptamer;    EpCAM;   

Others  :  1139194
DOI  :  10.1186/s12929-014-0108-9

 received in 2014-10-14, accepted in 2014-12-19,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Subramanian et al.; licensee BioMed Central.

【 图 表 】

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