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

• Published in: Nanomedicine Vol. 14; no. 3; pp. 769 - 780
• Main Authors: Qi, Bowen, Crawford, Ayrianne J., Wojtynek, Nicholas E., Holmes, Megan B., Souchek, Joshua J., Almeida-Porada, Graca, Ly, Quan P., Cohen, Samuel M., Hollingsworth, Michael A., Mohs, Aaron M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2018
• Subjects: Animals; Carcinoma, Pancreatic Ductal - diagnostic imaging; Carcinoma, Pancreatic Ductal - pathology; Carcinoma, Pancreatic Ductal - surgery; Chemotaxis; Disease Models, Animal; Female; Fluorescence; Fluorescence image-guided surgery; Hyaluronic acid; Hyaluronic Acid - chemistry; Indocyanine green; Indocyanine Green - administration & dosage; Indocyanine Green - metabolism; Mice; Mice, Inbred C57BL; Microscopy, Fluorescence; Nanoparticles - administration & dosage; Nanoparticles - metabolism; Optical Imaging - methods; Pancreatic ductal adenocarcinoma; Pancreatic Neoplasms - diagnostic imaging; Pancreatic Neoplasms - pathology; Pancreatic Neoplasms - surgery; Phagocytosis; Splenic metastasis; Surgery, Computer-Assisted - methods; Tumor Cells, Cultured; Fluorescence image-guided surgery; DMSO; ALP; EPR; ALT; Indocyanine green; NIRF; IFSC; RES system; RBC; CCK-8; HPNE; US; HGB; H&E; uPA; ROI; AMY; CAM; MMP; Splenic metastasis; PDAC; AU; HCT; Hyaluronic acid; HA-PBA; MRI; TPC; FIGS; SD; SNR; WBC; PLT; GLOB; BUN; GI tract; EGF; Pancreatic ductal adenocarcinoma; ICG; CT; ATF; HMW; NanoICG; NIR; LMW; ALB; HA; TP; PET; KPC
• ISSN: 1549-9634; 1549-9642; 1549-9642
• DOI: 10.1016/j.nano.2017.12.015

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. A hyaluronic acid nanoformulation of indocyanine green (NanoICG) contrast-enhanced pancreatic ductal adenocarcinoma (PDAC) during surgical navigation and ex vivo analysis. The enhancement of the syngeneic, orthotopic PDAC was significantly higher compared to adjacent healthy pancreas and compared to tumor enhanced by ICG alone. [Display omitted]