Theranostics 2019; 9(3):837-852. doi:10.7150/thno.30228

Research Paper

Anti-EGF Receptor Aptamer-Guided Co-Delivery of Anti-Cancer siRNAs and Quantum Dots for Theranostics of Triple-Negative Breast Cancer

Min Woo Kim1,2, Hwa Yeon Jeong1, Seong Jae Kang1, In Ho Jeong1, Moon Jung Choi1, Young Myoung You1, Chan Su Im1, In Ho Song4, Tae Sup Lee4, Jin Suk Lee5, Aeju Lee2,3, Yong Serk Park1✉

1. Department of Biomedical Laboratory Science, Yonsei University, Wonju, Republic of Korea
2. International Research Organization for Advance Science and Technology (IROAST), Kumamoto University, Kumamoto, Japan
3. Magnesium Research Center, Kumamoto University, Kumamoto, Japan
4. Division of RI-Convergence Research, Korea Institute of Radiological and Medical Science, Seoul, Republic of Korea
5. Department of Anatomy, Yonsei University Wonju Collage of Medicine, Wonju, Republic of Korea

Abstract

Many aptamers have been evaluated for their ability as drug delivery vehicles to target ligands, and a variety of small interfering RNAs (siRNAs) have been tested for their anti-cancer properties. However, since these two types of molecules have similar physicochemical properties, it has so far been difficult to formulate siRNA-encapsulating carriers guided by aptamers. Here, we propose aptamer-coupled lipid nanocarriers encapsulating quantum dots (QDs) and siRNAs for theragnosis of triple-negative breast cancer (TNBC).

Methods: Hydrophobic QDs were effectively incorporated into lipid bilayers, and then therapeutic siRNAs were complexed with QD-lipid nanocarriers (QLs). Finally, anti-EGFR aptamer-lipid conjugates were inserted into the QLs for TNBC targeting (aptamo-QLs). TNBC-targeting aptamo-QLs were directly compared to anti-EGFR antibody-coupled immuno-QLs. The in vitro delivery of therapeutic siRNAs and QDs to target cells was assessed by flow cytometry and confocal microscopy. The in vivo targeting of siRNAs to tumors and their therapeutic efficacy were evaluated in mice carrying MDA-MB-231 tumors.

Results: Both types of EGFR-targeting QLs showed enhanced delivery to target cancer cells, resulting in more effective gene silencing and enhanced tumor imaging compared to non-targeting control QLs. Moreover, combinatorial therapy with Bcl-2 and PKC-ι siRNAs loaded into the anti-EGFR QLs was remarkably effective in inhibiting tumor growth and metastasis.

Conclusion: In general, the aptamo-QLs showed competitive in vivo delivery and therapeutic efficacy compared to immuno-QLs under the same experimental conditions. Our results show that the anti-EGFR aptamer-guided lipid carriers may be a potential theranostic delivery vehicle for RNA interference and fluorescence imaging of TNBCs.

Keywords: nanotheranostics, anti-EGFR aptamer, lipid nanocarriers, quantum dots, gene therapy

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How to cite this article:
Kim MW, Jeong HY, Kang SJ, Jeong IH, Choi MJ, You YM, Im CS, Song IH, Lee TS, Lee JS, Lee A, Park YS. Anti-EGF Receptor Aptamer-Guided Co-Delivery of Anti-Cancer siRNAs and Quantum Dots for Theranostics of Triple-Negative Breast Cancer. Theranostics 2019; 9(3):837-852. doi:10.7150/thno.30228. Available from http://www.thno.org/v09p0837.htm