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

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.

Hyaluronic acid formulation of near infrared fluorophores optimizes surgical imaging in a prostate tumor xenograft

“…Necropsied tissue was subjected to additional spectroscopic analysis. Spectra from tissues were obtained with the tip of the laser 1 cm from the tissue surface, with laser power at 30 mW or 80 mW, and results were normalized, which is consistent with our previously reported methods [23,29,32,34]. …”

“…In pancreatic tumors, NanoICG PBA signal was 2.0 times that of the ICG group [32]. Thus, the contrast ratios compared to muscle are consistently about 2-fold higher for NanoICG PBA .…”

“…Prior to TEM imaging, NPs (concentration 1.0 mg/mL in PBS) were placed on a formvar/silicone monoxide-coated 200 mesh copper grid and allowed to adhere for approximately 5 min, NanoVan negative stain was applied for 30 s, and the sample was blotted to remove excess solvent or material. TEM images of NanoICG and NanoCy7.5 10k-PBA NPs are also provided in our previous publications [23,32,33]. The stability of NanoICG PBA in a solution of PBS containing bovine serum albumin (BSA) has been reported [23], showing that ICG was rapidly released into albumin-containing solution across a dialysis membrane.…”

Solubilization of Hexyl Aminolevulinate by Surfactants for Tumor Fluorescence Detection

“…Fluorescence imaging methods have received tremendous attention for use in real‐time image‐guided surgery (34). Several fluorescent agents have been reported for pancreatic cancer imaging (35–37). Compared with those naturally fluorescent molecules, ALA could provide highly selective tumor fluorescence imaging because tumoral cells tend to exhibit higher levels of PpIX than normal cells after ALA administration (38,39).…”

Spotting Brain and Pancreatic Tumor Identification Through SRM Segmentation and Naive Bayes Method

“…Clinically obtainable imaging preoperative modalities, CT image' serious to clinical forecasting. Nevertheless, interpreting these consequences to the effective room is hard due to reformed body locating, tissue operation, and absence of sensitivity to sense microscopic wounds [4].…”