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

Abstract

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.

Functional intercalated nanocomposites with chitosan-glutathione-glycylsarcosine and layered double hydroxides for topical ocular drug delivery

“…Other previous report also showed that dipeptide Ser-Glu had high specificity to PepT-1, which could act as an active target ligand to functionalize nanoparticles for tumor-targeted drug delivery. 48 Overall, these results confirmed that the active transport by PepT-1 and clathrin-mediated endocytosis might be involved in the cellular uptake of CG-GS-LDH nanocomposites.…”

Current status of targeted microbubbles in diagnostic molecular imaging of pancreatic cancer

“…Numerous rodent models have contributed to the understanding of PDAC pathogenesis and thereby, provided opportunities to characterize and detect disease progression from benign to malignant stages with imaging tools. AsPC-1, 105,115 BxPC-3, 47,92,113 Capan-1, 117 Capan-2, 102,110,120 COLO-357, 94,97 MIA PaCa-2, 74,106 Panc-1 95,129 and PL45 cells 108 (KPC) 89,124 and Pdx-1-Cre; LSL-Kras G12D/+ ; Ink4a/Arf −/− . 16,[71][72][73]104 Last mentioned model has been utilized in molecular ultrasound imaging due to the expression of Thy1 or VEGFR2 on its tumor neovasculature.…”

“…With the aim of producing high fidelity, preclinical models representative of the architectural and functional complexity of human PDAC, various mouse models including carcinogen-induced and genetically engineered murine pancreatic tumor models have been currently employed for preclinical ultrasound imaging researches. AsPC-1, 105,115 BxPC-3, 47,92,113 Capan-1, 117 Capan-2, 102,110,120 COLO-357, 94,97 MIA PaCa-2, 74,106 Panc-1 95,129 and PL45 cells 108 Compared to the CDX models, PDXs are created by transplanting a piece of patient tumor tissue derived from surgical resection or from tumor biopsies, in immunodeficient mice. 90 Such tissues can be obtained during EUS-FNA.…”

Effect of biphenyl hydrolase-like (BPHL) gene disruption on the intestinal stability, permeability and absorption of valacyclovir in wildtype and Bphl knockout mice

“…Along with other prodrug targeted transporters, such as the organic anion transporter (OAT) family and the organic cation transporter (OCT) family, the PepT1 transporter is predominately expressed on the apical membrane of enterocytes and its biochemistry, biology, pharmacokinetics and substrate specificity have been well characterized [19–23]. As such, PepT1 is a potential drug design target for improving intestinal absorption and the systemic availability of poorly absorbed drug molecules [4,24,25]. In addition to increasing oral drug absorption, an essential step is the conversion of prodrug to its active therapeutic moiety.…”