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

Ma, Jingbo1,2; Xu, Xiaolong3; Fu, Chunjin3; Xia, Peng1,4; Tian, Ming1,4; Zheng, Liuhai1; Chen, Kun1; Liu, Xiaolian5; Li, Yilei5; Yu, Le5,6; Zhu, Qinchang7; Yu, Yangyang8; Fan, Rongrong9; Jiang, Haibo10; Li, Zhifen11; Yang, Chuanbin3; Xu, Chengchao3; Long, Ying1; Wang, Jigang3,6,12,13; Li, Zhijie1,3

2022-11-26

10.1186/s40824-022-00312-3

Biomaterials Research   影响因子和分区

1226-4601

2055-7124

["Background: 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.","Methods: Naive 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.","Results: Two nanobodies (Al 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.","Conclusions: 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."]

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

SCI

英语

第一 ; 通讯

Basic and Applied Basic Research Foundation of GuangDong Province["2021A1515012164","2021A1515111188"] ; International Science and Technology Cooperation for Shenzhen Technology Innovation Plan[GJHZ20200731095411034] ; National Key Research and Development Program of China["2020YFA0908000","2022YFC2303600"] ; Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine[ZYYCXTDC-202002] ; Shenzhen Science and Technology Innovation Commission["JCYJ20210324115800001","JCYJ20210324114014039"] ; National Natural Science Foundation of China["82074098","81841001","82274182"]

Engineering ; Materials Science

Engineering, Biomedical ; Materials Science, Biomaterials

WOS:000888816400002

SPRINGERNATURE

Web of Science

1.Jinan Univ, Southern Univ Sci & Technol, Affiliated Hosp 1, Dept Hyperbar Med,Shenzhen Peoples Hosp,Clin Med, Shenzhen 518020, Guangdong, Peoples R China
2.Tianjin Univ Tradit Chinese Med, Coll Tradit Chinese Med, Tianjin 300193, Peoples R China
3.Jinan Univ, Southern Univ Sci & Technol, Affiliated Hosp 1, Dept Geriatr,Shenzhen Peoples Hosp,Clin Med Coll, Shenzhen 518020, Guangdong, Peoples R China
4.Wuhan Univ, Dept Hepatobiliary & Pancreat Surg, Zhongnan Hosp, Wuhan 430072, Hubei, Peoples R China
5.Southern Med Univ, Nanfang Hosp, Clin Pharm Ctr, Guangzhou 510515, Guangdong, Peoples R China
6.Southern Med Univ, Sch Pharmaceut Sci, Guangdong Prov Key Lab New Drug Screening, Guangzhou 510515, Guangdong, Peoples R China
7.Shenzhen Technol Univ, Coll Pharm, Shenzhen 518118, Peoples R China
8.Shenzhen Univ, Hlth Sci Ctr, Shenzhen 518055, Guangdong, Peoples R China
9.Karolinska Inst, Dept Biosci & Nutr, S-14157 Stockholm, Sweden
10.Univ Hong Kong, Dept Chem, Pok Fu Lam, Hong Kong, Peoples R China
11.Shanxi Datong Univ, Sch Chem & Chem Engn, Xing Yun St, Datong 037009, Shanxi, Peoples R China
12.China Acad Chinese Med Sci, Artemisinin Res Ctr, Beijing 100700, Peoples R China
13.China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing 100700, Peoples R China

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).

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).

Ma, Jingbo,et al."CDH17 nanobodies facilitate rapid imaging of gastric cancer and efficient delivery of immunotoxin".Biomaterials Research 26.1(2022).