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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.
Abstract:
A current challenge in the treatment of peritoneal carcinomatosis is the inability to detect, visualize, and resect small or microscopic tumors of pancreatic, ovarian, or mesothelial origin. In these diseases, the completeness of primary tumor resection is directly correlated with patient survival, and hence, identifying small sub-millimeter tumors (i.e., disseminated disease) is critical. Thus, new imaging techniques and probes are needed to improve cytoreductive surgery and patient outcomes. Highly fluorescent rhodamine-labeled expansile nanoparticles (HFR-eNPs) are described for use as a visual aid during cytoreductive surgery of pancreatic carcinomatosis. The covalent incorporation of rhodamine into ∼30 nm eNPs increases the fluorescent signal compared to free rhodamine, thereby affording a brighter and more effective probe than would be achieved by a single rhodamine molecule. Using the intraperitoneal route of administration, HFR-eNPs localize to regions of large (∼1 cm), sub-centimeter, and sub-millimeter intraperitoneal tumor in three different animal models, including pancreatic, mesothelioma, and ovarian carcinoma. Tumoral localization of the HFR-eNPs depends on both the material property (i.e., eNP polymer) as well as the surface chemistry (anionic surfactant vs PEGylated noncharged surfactant). In a rat model of pancreatic carcinomatosis, HFR-eNP identification of tumor is validated against gold-standard histopathological analysis to reveal that HFR-eNPs possess high specificity (99%) and sensitivity (92%) for tumors, in particular, sub-centimeter and microscopic sub-millimeter tumors, with an overall accuracy of 95%. Finally, as a proof-of-concept, HFR-eNPs are used to guide the resection of pancreatic tumors in a rat model of peritoneal carcinomatosis.
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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