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Ets1 identified as a novel molecular target of RNA aptamer selected against metastatic cells for targeted delivery of nano-formulation

Oncogene volume 34, pages 5216–5228 (2015)Cite this article

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Abstract

Nanomedicine era is not far from its realization, but a major concern of targeted delivery still stands tall in its way. Herein we demonstrate the mechanism underlying the anticancer activity of an RNA aptamer (Apt) conjugated to gefitinib-loaded poly (lactic co-glycolic acid) nanoparticles (GNPs). Apt was selected through Cell-SELEX (systemic evolution of ligands by exponential enrichment) process against gefitinib-resistant H1975 lung cancer cells. The selected aptamer exhibited high specificity toward H1975 cells, both qualitatively as well as quantitatively. Software analysis using the MATCH tool predicted Ets1, a proto-oncoprotein, to be the target of the selected aptamer. Interestingly, the localization of identified aptamer varied in descending order of Ets1 expression, wherein maximum localization was observed in H1975 cells than in MDA-MB231, DU-145, H23, H460, A431, A549 and MCF-7 cells, and minimum in L132 cells. Furthermore, Apt-GNP bio-conjugate showed augmented anticancer activity specifically in Ets1-overexpressing cells. In addition, partial depletion of Ets1 in H1975 cells and overexpression of Ets1 in L132 cells reversed the targeting efficacy of the aptamer. Notably, a single intratumoral injection of the Apt-GNP bio-conjugate abrogated the growth of tumor in H1975 xenograft nude mice. Altogether, we present a pioneering platform, involving aptamers, which can be clinically used as a diagnostic marker for metastasis as well as an effective delivery system to escort the pharmaceutical cargo specifically to Ets1-overexpressing highly progressive tumors.

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Acknowledgements

The intellectual property rights of the above described delivery system comprising of the aptamer-NP bio-conjugate are protected under Indian Patent Office (Indian Patent application no: 1623/DEL/2014).

Author Contributions

JK designed, performed the experiments and analyzed the data. KT designed, supervised and approved the final version of manuscript.

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  1. Department of Pharmacology and Toxicology, Laboratory of Epigenetics and Diseases, National Institute of Pharmaceutical Education and Research, SAS Nagar (formerly Mohali), Punjab, India

    J Kaur & K Tikoo

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  1. J Kaur
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Correspondence to K Tikoo.

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The authors declare no conflict of interest.

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Supplementary Information accompanies this paper on the Oncogene website

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Kaur, J., Tikoo, K. Ets1 identified as a novel molecular target of RNA aptamer selected against metastatic cells for targeted delivery of nano-formulation. Oncogene 34, 5216–5228 (2015). https://doi.org/10.1038/onc.2014.447

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