A new target ligand Ser-Glu for PEPT1-overexpressing cancer imaging

• Published in: International journal of nanomedicine 2016-01, Vol.11 (Issue 1), p.203-212
• Main Authors: Dai, Tongcheng, Li, Na, Zhang, Lingzhi, Zhang, Yuanxing, Liu, Qin
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - drug effects; Biomarkers; Blotting, Western; Cancer; Cell culture; Cell Proliferation - drug effects; Dipeptides - chemistry; Dipeptides - pharmacology; Drug delivery systems; Female; Flow Cytometry; Fluorescence; Glutamic Acid - chemistry; Humans; Image Processing, Computer-Assisted; imaging; Kidneys; Laboratories; Ligands; Mice; Mice, Inbred BALB C; Mice, Nude; Nanoparticles; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Original Research; Pancreatic cancer; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; PEPT1 transporter; Peptide Transporter 1; Peptides; Polymers - chemistry; Proteins; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Ser-Glu; Serine - chemistry; Symporters - antagonists & inhibitors; Symporters - genetics; Symporters - metabolism; target ligand; Tumor Cells, Cultured; Xenograft Model Antitumor Assays
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S97207

Nanoparticles functionalized with active target ligands have been widely used for tumor-specific diagnosis and therapy. The target ligands include antibodies, peptides, proteins, small molecules, and nucleic acid aptamers. Here, we utilize dipeptide Ser-Glu (DIP) as a new ligand to functionalize polymer-based fluorescent nanoparticles (NPs) for pancreatic cancer target imaging. We demonstrate that in the first step, Ser-Glu-conjugated NPs (NPs-DIP) efficiently bind to AsPC-1 and in the following NPs-DIP are internalized into AsPC-1 in vitro. The peptide transporter 1 inhibition experiment reveals that the targeting effects mainly depend on the specific binding of DIP to peptide transporter 1, which is remarkably upregulated in pancreatic cancer cells compared with varied normal cells. Furthermore, NPs-DIP specifically accumulate in the site of pancreatic tumor xenograft and are further internalized into the tumor cells in vivo after intravenous administration, indicating that DIP successfully enhanced nanoparticles internalization efficacy into tumor cells in vivo. This work establishes Ser-Glu to be a new tumor-targeting ligand and provides a promising tool for future tumor diagnostic or therapeutic applications.