title: RGD Peptide Cell-Surface Display Enhances the Targeting and Therapeutic Efficacy of Attenuated Salmonella-mediated Cancer Therapy.
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.
authors.affiliation: 1. Department of Nuclear Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea;; 6. Biological Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeongeup, Republic of Korea.
authors.forename: Seung-Hwan
authors.initials: SH
authors.lastname: Park
authors.affiliation: 1. Department of Nuclear Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea;
authors.forename: Jin Hai
authors.initials: JH
authors.lastname: Zheng
authors.affiliation: 1. Department of Nuclear Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea;
authors.forename: Vu Hong
authors.initials: VH
authors.lastname: Nguyen
authors.affiliation: 3. Department of Nuclear Medicine, Haikou Hospital Affiliated to Xiangya School of Medicine, Central South University, China;
authors.forename: Sheng-Nan
authors.initials: SN
authors.lastname: Jiang
authors.affiliation: 1. Department of Nuclear Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea;
authors.forename: Dong-Yeon
authors.initials: DY
authors.lastname: Kim
authors.affiliation: 4. Fraunhofer IZI, Leipzig, Germany;
authors.forename: Michael
authors.initials: M
authors.lastname: Szardenings
authors.affiliation: 5. Department of Biology, Kyung Hee University College of Science, Seoul, Republic of Korea;
authors.forename: Jung Hyun
authors.initials: JH
authors.lastname: Min
authors.affiliation: 2. Department of Microbiology, Chonnam National University Medical School, Gwangju, Republic of Korea;
authors.forename: Yeongjin
authors.initials: Y
authors.lastname: Hong
authors.affiliation: 2. Department of Microbiology, Chonnam National University Medical School, Gwangju, Republic of Korea;
authors.forename: Hyon E
authors.initials: HE
authors.lastname: Choy
authors.affiliation: 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;
authors.forename: Jung-Joon
authors.initials: JJ
authors.lastname: Min
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001422:Bacterial Adhesion; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics; D001943:Breast Neoplasms / Q000628:therapy*; D061505:Cell Surface Display Techniques; D004195:Disease Models, Animal; D004337:Drug Carriers; D064593:Heterografts; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D008545:Melanoma / Q000628:therapy*; D051379:Mice; D009842:Oligopeptides / Q000235:genetics / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology; D012486:Salmonella typhimurium / Q000235:genetics* / Q000502:physiology; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001425:Bacterial Outer Membrane Proteins; D004337:Drug Carriers; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D011993:Recombinant Fusion Proteins; C078167:OMPA outer membrane proteins; C047981:arginyl-glycyl-aspartic acid
keywords: RGD peptide; Salmonella typhimurium; bacteria-mediated cancer therapy; bioluminescence imaging.; surface display