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CDH17 nanobodies facilitate rapid imaging of gastric cancer and efficient delivery of immunotoxin

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收录情况： ◇ SCIE

作者：
Ma Jingbo[1,2] * ; Xu Xiaolong[3] * ; Fu Chunjin[3] * ; Xia Peng[1,4] ; Tian Ming[1,4] ; Zheng Liuhai[1] ; Chen Kun[1] ; Liu Xiaolian[5] ; Li Yilei[5] ; Yu Le[5,6] ; Zhu Qinchang[7] ; Yu Yangyang[8] ; Fan Rongrong[9] ; Jiang Haibo[10] ; Li Zhifen[11] ; Yang Chuanbin[3] ; Xu Chengchao[3] ; Long Ying[1] ; Wang Jigang[3,6,12] ; Li Zhijie[1,3] ;
机构： [1]Department of Hyperbaric Medicine, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Afliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, P. R. China. [2]College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, P. R. China. [3]Department of Geriatrics, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Afliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, P. R. China. [4]Department of Hepatobiliary & Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430072, Hubei, P. R. China. [5]Clinical Pharmacy Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, P. R. China. [6]Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, Guangdong, P.R. China. [7]College of Pharmacy, Shenzhen Technology University, Shenzhen 518118, P.R. China. [8]Health Science Center, Shenzhen University, Shenzhen 518055, Guangdong, P. R. China. [9]Deapartment of Biosciences and Nutrition, Karolinska Institute, 14157 Stockholm, Sweden. [10]Department of Chemistry, The University of Hong Kong, Pok Fu Lam, Hong Kong, P. R. China. [11]School of Chemistry and Chemical Engineering, Shanxi Datong University, Xing Yun Street, Pingcheng District, Datong 037009, Shanxi, P. R. China. [12]Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, P. R. China.
出处：
DOI： 10.1186/s40824-022-00312-3
ISSN：

关键词： Nanobody Cadherin-17 Immunotoxin Gastric cancer Targeted therapy Jingbo Ma Xiaolong Xu and Chunjin Fu are contribute equally to this work and share the frst-authorship

摘要：
It is highly desirable to develop new therapeutic strategies for gastric cancer given the low survival rate despite improvement in the past decades. Cadherin 17 (CDH17) is a membrane protein highly expressed in cancers of digestive system. Nanobody represents a novel antibody format for cancer targeted imaging and drug delivery. Nanobody targeting CHD17 as an imaging probe and a delivery vehicle of toxin remains to be explored for its theragnostic potential in gastric cancer.Naïve nanobody phage library was screened against CDH17 Domain 1-3 and identified nanobodies were extensively characterized with various assays. Nanobodies labeled with imaging probe were tested in vitro and in vivo for gastric cancer detection. A CDH17 Nanobody fused with toxin PE38 was evaluated for gastric cancer inhibition in vitro and in vivo.Two nanobodies (A1 and E8) against human CDH17 with high affinity and high specificity were successfully obtained. These nanobodies could specifically bind to CDH17 protein and CDH17-positive gastric cancer cells. E8 nanobody as a lead was extensively determined for tumor imaging and drug delivery. It could efficiently co-localize with CDH17-positive gastric cancer cells in zebrafish embryos and rapidly visualize the tumor mass in mice within 3 h when conjugated with imaging dyes. E8 nanobody fused with toxin PE38 showed excellent anti-tumor effect and remarkably improved the mice survival in cell-derived (CDX) and patient-derived xenograft (PDX) models. The immunotoxin also enhanced the anti-tumor effect of clinical drug 5-Fluorouracil.The study presents a novel imaging and drug delivery strategy by targeting CDH17. CDH17 nanobody-based immunotoxin is potentially a promising therapeutic modality for clinical translation against gastric cancer.© 2022. The Author(s).

基金：
This work was supported by Basic and Applied Basic Research Foundation of GuangDong Province (2021A1515012164) to Z.J.L and (2021A1515111188) to X.L.X, International Science and Technology Cooperation for Shenzhen Technology Innovation Plan (GJHZ20200731095411034) to Z.J.L. and R.R.F., National Key Research and Development Program of China (2020YFA0908000, 2022YFC2303600) to J.G.W., Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine (ZYYCXTDC-202002) to J.G.W., National Natural Science Foundation of China (82074098, 81841001, 82274182) to J.G.W., Shenzhen Science and Technology Innovation Commission (JCYJ20210324115800001 and JCYJ20210324114014039) to J.G.W..
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大类 | 2 区 医学
小类 | 2 区 工程：生物医学 2 区 材料科学：生物材料
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出版当年[2020]版：
无
最新[2023]版：
Q1 ENGINEERING, BIOMEDICAL Q1 MATERIALS SCIENCE, BIOMATERIALS

影响因子： 最新[2023版] 最新五年平均 出版当年[2020版] 出版当年五年平均 出版前一年[2019版] 出版后一年[2021版]

第一作者：
第一作者机构： [1]Department of Hyperbaric Medicine, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Afliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, P. R. China. [2]College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, P. R. China.
共同第一作者：
通讯作者：
通讯机构： [1]Department of Hyperbaric Medicine, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Afliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, P. R. China. [3]Department of Geriatrics, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Afliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, P. R. China. [6]Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, Guangdong, P.R. China. [12]Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, P. R. China.
推荐引用方式(GB/T 7714)：
Ma Jingbo,Xu Xiaolong,Fu Chunjin,et al.CDH17 nanobodies facilitate rapid imaging of gastric cancer and efficient delivery of immunotoxin[J].BIOMATERIALS RESEARCH.2022,26(1):doi:10.1186/s40824-022-00312-3.
APA：
Ma Jingbo,Xu Xiaolong,Fu Chunjin,Xia Peng,Tian Ming...&Li Zhijie.(2022).CDH17 nanobodies facilitate rapid imaging of gastric cancer and efficient delivery of immunotoxin.BIOMATERIALS RESEARCH,26,(1)
MLA：
Ma Jingbo,et al."CDH17 nanobodies facilitate rapid imaging of gastric cancer and efficient delivery of immunotoxin".BIOMATERIALS RESEARCH 26..1(2022)

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