title: Highly Specific and Sensitive Fluorescent Nanoprobes for Image-Guided Resection of Sub-Millimeter Peritoneal Tumors.
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.
authors.affiliation: Departments of Biomedical Engineering and Chemistry, Boston University , Boston, Massachusetts 02215, United States.|Division of Thoracic Surgery, Department of Surgery, Brigham and Women's Hospital , Boston, Massachusetts 02115, United States.
authors.forename: Aaron H
authors.initials: AH
authors.lastname: Colby
authors.affiliation: Departments of Biomedical Engineering and Chemistry, Boston University , Boston, Massachusetts 02215, United States.
authors.forename: Samantha M
authors.initials: SM
authors.lastname: Berry
authors.affiliation: Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine , Boston, Massachusetts 02118, United States.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Moran
authors.affiliation: Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine , Boston, Massachusetts 02118, United States.
authors.forename: Kristine Amber
authors.initials: KA
authors.lastname: Pasion
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, Brigham and Women's Hospital , Boston, Massachusetts 02115, United States.
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, Brigham and Women's Hospital , Boston, Massachusetts 02115, United States.
authors.forename: Yolonda L
authors.initials: YL
authors.lastname: Colson
authors.affiliation: Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine , Boston, Massachusetts 02118, United States.
authors.forename: Nelson
authors.initials: N
authors.lastname: Ruiz-Opazo
authors.affiliation: Departments of Biomedical Engineering and Chemistry, Boston University , Boston, Massachusetts 02215, United States.|Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine , Boston, Massachusetts 02118, United States.
authors.forename: Mark W
authors.identifier: 0000-0002-5453-3668
authors.initials: MW
authors.lastname: Grinstaff
authors.affiliation: Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine , Boston, Massachusetts 02118, United States.
authors.forename: Victoria L M
authors.initials: VL
authors.lastname: Herrera
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003131:Combined Modality Therapy; D065426:Cytoreduction Surgical Procedures; D004195:Disease Models, Animal; D005260:Female; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D007274:Injections, Intraperitoneal; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000601:surgery; D008654:Mesothelioma / Q000000981:diagnostic imaging* / Q000601:surgery; D000086002:Mesothelioma, Malignant; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D061848:Optical Imaging; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging* / Q000601:surgery; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging* / Q000601:surgery; D010534:Peritoneal Neoplasms / Q000000981:diagnostic imaging* / Q000601:surgery; D051381:Rats; D012235:Rhodamines / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D013501:Surface-Active Agents / Q000737:chemistry; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
chemical_list: D005456:Fluorescent Dyes; D012235:Rhodamines; D013501:Surface-Active Agents
keywords: expansile nanoparticles; fluorescent nanoparticle probes; fluorescently guided resection; pancreatic cancer; peritoneal carcinomatosis