Plectin-1 Targeted Agents for Detection and Treatment of Pancreatic Ductal Adenocarcinoma

Abstract

Described herein are compositions and methods for cancer cell biomarkers, such as pancreatic ductal adenocarcinoma (PDAC) cell biomarkers, and binding molecules for diagnosis and treatment of cancer, e.g., PDAC. Methods of identifying “accessible” proteomes are disclosed for identifying cancer biomarkers, such as plectin-1, a PDAC biomarker. Additionally, imaging compositions are provided comprising magnetofluorescent nanoparticies conjugated to peptide ligands for identifying PDACs.

1 . A peptide ligand comprising:
 a first portion comprising a plectin-1 binding moiety, coupled to   a second portion comprising a detectable moiety or a therapeutic agent.   
     
     
         2 . The peptide ligand of  claim 1 , wherein the plectin-1 binding moiety is an amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 2, or 4-8, or a peptidomimetic thereof. 
     
     
         3 . The peptide ligand of  claim 1 , wherein the detectable moiety is selected from the group consisting of a radioactive isotope, a magnetic compound, an x-ray absorber, a chemical compound, a biological tag, and a fluorescent molecule. 
     
     
         4 . The peptide ligand of  claim 1 , wherein the therapeutic agent is a cytotoxic moiety or an immunomodulatory moiety. 
     
     
         5 . The peptide ligand of  claim 1 , further comprising a linker between the first portion and the second portion. 
     
     
         6 . The peptide ligand of  claim 5 , wherein the linker is a flexible amino acid sequence. 
     
     
         7 . The peptide ligand of  claim 4 , wherein the linker is a photolinker. 
     
     
         8 . The peptide ligand of  claim 1 , wherein the second portion further comprises a physiologically inert nanoparticle. 
     
     
         9 . The peptide ligand of  claim 8 , wherein the nanoparticle is magnetic, fluorescent, or radioactive. 
     
     
         10 . The peptide ligand of  claim 1 , wherein the second portion comprises a fluorochrome. 
     
     
         11 . The peptide ligand of  claim 10 , wherein the fluorochrome is a near infrared fluorochrome. 
     
     
         12 . The peptide ligand of  claim 1 , wherein the second portion comprises a crosslinked iron oxide nanoparticle conjugated to a NIRF. 
     
     
         13 . A peptide ligand comprising SEQ ID NO:1 coupled to a nanoparticle. 
     
     
         14 . The peptide ligand of  claim 13 , wherein the magnetofluorescent nanoparticle comprises a near infrared (NIR) fluorochrome (NIRF). 
     
     
         15 . A method for the treatment of pancreatic ductal adenocarcinoma, the method comprising administering the peptide ligand of  claim 1 .