Targeting Pancreatic Cancer Cells with Peptide-Functionalized Polymeric Magnetic Nanoparticles

Int J Mol Sci. 2019 Jun 19;20(12):2988. doi: 10.3390/ijms20122988.

Abstract

Pancreatic cancer is a concealed and highly malignant tumor, and its early diagnosis plays an increasingly weighty role during the course of cancer treatment. In this study, we developed a polymeric magnetic resonance imaging (MRI) nanoplatform for MRI contrast agents. To improve tumor-targeting delivery of MRI contrast agents, we employed a pancreatic cancer targeting CKAAKN peptide to prepare a peptide-functionalized amphiphilic hyaluronic acid-vitamin E succinate polymer (CKAAKN-HA-VES) for delivering ultra-small superparamagnetic iron oxide (USPIO), namely, CKAAKN-HA-VES@USPIO. With the modification of the CKAAKN peptide, CKAAKN-HA-VES@USPIO could specifically internalize into CKAAKN-positive BxPC-3 cells. The CKAAKN-HA-VES@USPIO nanoparticles presented a more specific accumulation into pancreatic cancer cells than normal pancreatic cells, and an obvious decrease in signal intensity was observed in CKAAKN-positive BxPC-3 cells, compared with CKAAKN-negative HPDE6-C7 cells and non-targeting HA-VES@USPIO nanoparticles. The results demonstrated that our polymeric MRI nanoplatform could selectively internalize into CKAAKN-positive pancreatic cancer cells by the specific binding of CKAAKN peptide with pancreatic cancer cell membrane receptors, which provided a novel polymeric MRI contrast agent with high specificity for pancreatic cancer diagnosis, and makes it a very promising candidate for magnetic resonance imaging contrast enhancement.

Keywords: CKAAKN peptide; MRI contrast agent; pancreatic cancer; polymer.

MeSH terms

  • Biopolymers / chemistry*
  • Cell Line, Tumor
  • Cell Survival
  • Chemistry Techniques, Synthetic
  • Contrast Media / chemistry*
  • Humans
  • Magnetic Resonance Imaging / methods
  • Magnetite Nanoparticles / chemistry*
  • Magnetite Nanoparticles / ultrastructure
  • Molecular Structure
  • Pancreatic Neoplasms / diagnostic imaging
  • Peptides / chemistry*
  • Theranostic Nanomedicine* / methods

Substances

  • Biopolymers
  • Contrast Media
  • Magnetite Nanoparticles
  • Peptides