Theranostics 2016; 6(10):1672-1682. doi:10.7150/thno.16135

Research Paper

RGD Peptide Cell-Surface Display Enhances the Targeting and Therapeutic Efficacy of Attenuated Salmonella-mediated Cancer Therapy

Seung-Hwan Park1,6, Jin Hai Zheng1, Vu Hong Nguyen1, Sheng-Nan Jiang3, Dong-Yeon Kim1, Michael Szardenings4, Jung Hyun Min5, Yeongjin Hong2, Hyon E. Choy2✉, Jung-Joon Min1,2✉

1. Department of Nuclear Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea;
2. Department of Microbiology, Chonnam National University Medical School, Gwangju, Republic of Korea;
3. Department of Nuclear Medicine, Haikou Hospital Affiliated to Xiangya School of Medicine, Central South University, China;
4. Fraunhofer IZI, Leipzig, Germany;
5. Department of Biology, Kyung Hee University College of Science, Seoul, Republic of Korea;
6. Biological Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeongeup, Republic of Korea.

Abstract

Bacteria-based anticancer therapies aim to overcome the limitations of current cancer therapy by actively targeting and efficiently removing cancer. To achieve this goal, new approaches that target and maintain bacterial drugs at sufficient concentrations during the therapeutic window are essential. Here, we examined the tumor tropism of attenuated Salmonella typhimurium displaying the RGD peptide sequence (ACDCRGDCFCG) on the external loop of outer membrane protein A (OmpA). RGD-displaying Salmonella strongly bound to cancer cells overexpressing αvβ3, but weakly bound to αvβ3-negative cancer cells, suggesting the feasibility of displaying a preferential homing peptide on the bacterial surface. In vivo studies revealed that RGD-displaying Salmonellae showed strong targeting efficiency, resulting in the regression in αvβ3-overexpressing cancer xenografts, and prolonged survival of mouse models of human breast cancer (MDA-MB-231) and human melanoma (MDA-MB-435). Thus, surface engineering of Salmonellae to display RGD peptides increases both their targeting efficiency and therapeutic effect.

Keywords: Salmonella typhimurium, RGD peptide, bacteria-mediated cancer therapy, surface display, bioluminescence imaging.

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How to cite this article:
Park SH, Zheng JH, Nguyen VH, Jiang SN, Kim DY, Szardenings M, Min JH, Hong Y, Choy HE, Min JJ. RGD Peptide Cell-Surface Display Enhances the Targeting and Therapeutic Efficacy of Attenuated Salmonella-mediated Cancer Therapy. Theranostics 2016; 6(10):1672-1682. doi:10.7150/thno.16135. Available from http://www.thno.org/v06p1672.htm