Targeted Nanoparticles for Imaging Incipient Pancreatic Ductal Adenocarcinoma

Abstract

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) carries an extremely poor prognosis, typically presenting with metastasis at the time of diagnosis and exhibiting profound resistance to existing therapies. The development of molecular markers and imaging probes for incipient PDAC would enable earlier detection and guide the development of interventive therapies. Here we sought to identify novel molecular markers and to test their potential as targeted imaging agents. METHODS AND FINDINGS: Here, a phage display approach was used in a mouse model of PDAC to screen for peptides that specifically bind to cell surface antigens on PDAC cells. These screens yielded a motif that distinguishes PDAC cells from normal pancreatic duct cells in vitro, which, upon proteomics analysis, identified plectin-1 as a novel biomarker of PDAC. To assess their utility for in vivo imaging, the plectin-1 targeted peptides (PTP) were conjugated to magnetofluorescent nanoparticles. In conjunction with intravital confocal microscopy and MRI, these nanoparticles enabled detection of small PDAC and precursor lesions in engineered mouse models. CONCLUSIONS: Our approach exploited a well-defined model of PDAC, enabling rapid identification and validation of PTP. The developed specific imaging probe, along with the discovery of plectin-1 as a novel biomarker, may have clinical utility in the diagnosis and management of PDAC in humans.

Cited by papers we hold 3

• Clinical significance of circulating tumor cells after chemotherapy in unresectable pancreatic ductal adenocarcinoma · 2022
  Not checked
• Phage Ligands for Identification of Mesenchymal-Like Breast Cancer Cells and Cancer-Associated Fibroblasts · 2018
  Not checked
• Identification of the S100 fused-type protein hornerin as a regulator of tumor vascularity · 2017
  Not checked

Reads

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.