RGD peptide cell-surface display enhances the targeting and therapeutic efficacy of attenuated Salmonella-mediated cancer therapy

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Title
RGD peptide cell-surface display enhances the targeting and therapeutic efficacy of attenuated Salmonella-mediated cancer therapy
Author(s)
Seung Hwan Park; J H Zheng; V H Nguyen; S N Jiang; D Y Kim; M Szardenings; J H Min; Y Hong; Y E Choy; J J Min
Bibliographic Citation
Theranostics, vol. 6, no. 10, pp. 1672-1682
Publication Year
2016
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.
Keyword
Salmonella typhimuriumRGD peptidebacteria-mediated cancer therapysurface displaybioluminescence imaging.
ISSN
1838-7640
Publisher
Ivyspring Int Publ
DOI
http://dx.doi.org/10.7150/thno.16135
Type
Article
Appears in Collections:
Jeonbuk Branch Institute > Biological Resource Center > 1. Journal Articles
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