Ex vivo and in vivo capture and deactivation of circulating tumor cells by dual-antibody-coated nanomaterials.
Circulating tumor cells (CTCs) have been detected by us and others in cancer patient blood. However, little is known about how to specifically capture and deactivate CTCs in vivo, which may lead to successful metastasis prevention in asymptomatic cancer survivors after surgery. We hypothesize that the dual antibody conjugates may have the advantage of capturing CTCs specifically over their single antibody counterparts. Here we show that the surface-functionalized dendrimers can be sequentially coated with two antibodies directed to surface biomarkers (EpCAM and Slex) of human colorectal CTCs. The dual antibody-coated dendrimers exhibit a significantly enhanced specificity in capturing CTCs in the presence of interfering blood cells, and in both eight-patient bloods and nude mice administered with the labeled CTCs in comparison to their single antibody-coated counterparts. The dual antibody-coated conjugates down-regulate the captured CTCs. This study provides the first conceptual evidence that two antibodies can be biocompatibly conjugated to a nanomaterial to capture and down-regulate CTCs in vivo with the enhanced specificity.
Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350002, China.
Jingjing
J
Xie
Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350002, China.
Yu
Y
Gao
Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350002, China.
Rongli
R
Zhao
Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA.
Patrick J
PJ
Sinko
Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350002, China.
Songen
S
Gu
Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350002, China.
Jichuang
J
Wang
Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350002, China.
Yuanfang
Y
Li
Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350002, China.
Yusheng
Y
Lu
Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350002, China.
Suhong
S
Yu
Department of Surgery, East Hospital of Xiamen University, Fuzhou 350025, China.
Lie
L
Wang
Department of Surgery, East Hospital of Xiamen University, Fuzhou 350025, China.
Shuming
S
Chen
Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350002, China.
Jingwei
J
Shao
Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350002, China. Electronic address: jiali@fzu.edu.cn.
Lee
L
Jia
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000276:immunology* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism; D050091:Dendrimers / Q000737:chemistry; D000071858:Epithelial Cell Adhesion Molecule; D018922:HL-60 Cells; D019073:HT29 Cells; D006801:Humans; D008819:Mice, Nude; D049329:Nanostructures / Q000008:administration & dosage / Q000737:chemistry; D009360:Neoplastic Cells, Circulating / Q000187:drug effects* / Q000276:immunology; D009844:Oligosaccharides / Q000276:immunology* / Q000378:metabolism; D000080506:Sialyl Lewis X Antigen
D000906:Antibodies; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D050091:Dendrimers; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D009844:Oligosaccharides; C104700:PAMAM Starburst; D000080506:Sialyl Lewis X Antigen
Cancer metastasis; Capture efficiency; Capture specificity; Circulating tumor cells; Dual antibody conjugates