Highly Specific and Sensitive Fluorescent Nanoprobes for Image-Guided Resection of Sub-Millimeter Peritoneal Tumors

Aaron H Colby1,2, Samantha M Berry1, Ann M Moran3

  • 1Departments of Biomedical Engineering and Chemistry, Boston University , Boston, Massachusetts 02215, United States.

ACS Nano
|January 19, 2017
PubMed

Insights

Highly fluorescent rhodamine-labeled expansile nanoparticles (HFR-eNPs) effectively visualize small tumors during surgery. This new imaging probe improves detection of microscopic disease, enhancing surgical outcomes for peritoneal carcinomatosis.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Surgical Oncology

Background:

  • Peritoneal carcinomatosis presents a significant challenge due to difficulties in detecting and resecting small tumors.
  • Complete tumor resection is crucial for patient survival in pancreatic, ovarian, and mesothelial cancers.
  • Novel imaging agents are needed to enhance the visualization of microscopic disease during cytoreductive surgery.

Purpose of the Study:

  • To develop and evaluate highly fluorescent rhodamine-labeled expansile nanoparticles (HFR-eNPs) as a visual aid for cytoreductive surgery.
  • To assess the efficacy of HFR-eNPs in detecting various sizes of intraperitoneal tumors, including sub-millimeter lesions.
  • To validate the accuracy of HFR-eNPs in identifying tumors compared to histopathological analysis.

Main Methods:

  • Synthesis of rhodamine-labeled expansile nanoparticles (HFR-eNPs) with enhanced fluorescence.
  • Intraperitoneal administration of HFR-eNPs in three animal models (pancreatic, mesothelioma, ovarian carcinoma).
  • Evaluation of tumoral localization based on nanoparticle properties and surface chemistry.
  • Histopathological analysis to determine specificity, sensitivity, and accuracy of HFR-eNPs in tumor detection.
  • Proof-of-concept study using HFR-eNPs to guide tumor resection in a rat model.

Main Results:

  • HFR-eNPs demonstrated localization to large, sub-centimeter, and sub-millimeter intraperitoneal tumors.
  • Tumor detection accuracy was influenced by nanoparticle polymer and surface chemistry.
  • In a rat model, HFR-eNPs achieved 99% specificity and 92% sensitivity for tumor identification.
  • Overall accuracy for HFR-eNP tumor detection was 95%, particularly for small and microscopic tumors.
  • HFR-eNPs successfully guided the resection of pancreatic tumors in a proof-of-concept study.

Conclusions:

  • HFR-eNPs serve as a highly effective fluorescent probe for visualizing peritoneal carcinomatosis.
  • The nanoparticles significantly improve the detection of sub-millimeter and microscopic tumors, critical for complete resection.
  • HFR-eNPs show high accuracy and potential to enhance surgical outcomes in treating peritoneal carcinomatosis.

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