Indocyanine green loaded hyaluronan-derived nanoparticles for fluorescence-enhanced surgical imaging of pancreatic cancer

Nanomedicine. 2018 Apr;14(3):769-780. doi: 10.1016/j.nano.2017.12.015. Epub 2018 Jan 9.

Abstract

Pancreatic ductal adenocarcinoma is highly lethal and surgical resection is the only potential curative treatment for the disease. In this study, hyaluronic acid derived nanoparticles with physico-chemically entrapped indocyanine green, termed NanoICG, were utilized for intraoperative near infrared fluorescence detection of pancreatic cancer. NanoICG was not cytotoxic to healthy pancreatic epithelial cells and did not induce chemotaxis or phagocytosis, it accumulated significantly within the pancreas in an orthotopic pancreatic ductal adenocarcinoma model, and demonstrated contrast-enhancement for pancreatic lesions relative to non-diseased portions of the pancreas. Fluorescence microscopy showed higher fluorescence intensity in pancreatic lesions and splenic metastases due to NanoICG compared to ICG alone. The in vivo safety profile of NanoICG, including, biochemical, hematological, and pathological analysis of NanoICG-treated healthy mice, indicates negligible toxicity. These results suggest that NanoICG is a promising contrast agent for intraoperative detection of pancreatic tumors.

Keywords: Fluorescence image-guided surgery; Hyaluronic acid; Indocyanine green; Pancreatic ductal adenocarcinoma; Splenic metastasis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Pancreatic Ductal / diagnostic imaging
  • Carcinoma, Pancreatic Ductal / pathology
  • Carcinoma, Pancreatic Ductal / surgery
  • Chemotaxis
  • Disease Models, Animal
  • Female
  • Fluorescence
  • Hyaluronic Acid / chemistry*
  • Indocyanine Green / administration & dosage*
  • Indocyanine Green / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Fluorescence
  • Nanoparticles / administration & dosage*
  • Nanoparticles / metabolism
  • Optical Imaging / methods*
  • Pancreatic Neoplasms / diagnostic imaging
  • Pancreatic Neoplasms / pathology*
  • Pancreatic Neoplasms / surgery*
  • Phagocytosis
  • Surgery, Computer-Assisted / methods*
  • Tumor Cells, Cultured

Substances

  • Hyaluronic Acid
  • Indocyanine Green