title: Detection of fluorescent organic nanoparticles by confocal laser endomicroscopy in a rat model of Barrett's esophageal adenocarcinoma.
abstract: For many years, novel strategies for cancer detection and treatment using nanoparticles (NPs) have been developed. Esophageal adenocarcinoma is the sixth leading cause of cancer-related deaths in Western countries, and despite recent advances in early detection and treatment, its prognosis is still very poor. This study investigated the use of fluorescent organic NPs as potential diagnostic tool in an experimental in vivo model of Barrett's esophageal adenocarcinoma. NPs were made of modified polysaccharides loaded with [4-(dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran] (DCM), a well-known fluorescent dye. The NP periphery might or might not be decorated with ASYNYDA peptide that has an affinity for esophageal cancer cells. Non-operated and operated rats in which gastroesophageal reflux was surgically induced received both types of NPs (NP-DCM and NP-DCM-ASYNYDA) by intravenous route. Localization of mucosal NPs was assessed in vivo by confocal laser endomicroscopy, a technique which enables a "real time" and in situ visualization of the tissue at a cellular level. After injection of NP-DCM and NP-DCM-ASYNYDA, fluorescence was observed in rats affected by esophageal cancer, whereas no signal was observed in control non-operated rats, or in rats with simple esophagitis or Barrett's esophagus mucosa. Fluorescence was observable in vivo 30 minutes after the administration of NPs. Interestingly, NP-DCM-ASYNYDA induced strong fluorescence intensity 24 hours after administration. These observations suggested that NPs could reach the tumor cells, likely by enhanced permeability and retention effect, and the peptide ASYNYDA gave them high specificity for esophageal cancer cells. Thus, the combination of NP platform and confocal laser endomicroscopy could play an important role for highlighting esophageal cancer conditions. This result supports the potential of this strategy as a targeted carrier for photoactive and bioactive molecules in esophageal cancer diagnosis and treatment.
authors.affiliation: Department of Molecular Medicine, University of Padua, Padua, Italy ; Venetian Institute of Molecular Medicine, University of Padua, Padua, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Dassie
authors.affiliation: Venetian Institute of Molecular Medicine, University of Padua, Padua, Italy ; Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.
authors.forename: Diletta
authors.initials: D
authors.lastname: Arcidiacono
authors.affiliation: Faculty of Chemical and Process Engineering, Warsaw University of Technology, Warsaw, Poland.
authors.forename: Iga
authors.initials: I
authors.lastname: Wasiak
authors.affiliation: Department of Biomedical Sciences, University of Padua, Padua, Italy.
authors.forename: Nunzio
authors.initials: N
authors.lastname: Damiano
authors.affiliation: Department of Emergency Medicine, "Santi Giovanni e Paolo" Hospital, Venice, University of Padua, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Dall'Olmo
authors.affiliation: Anatomic Pathology Unit, ULSS 15, Alta Padovana, Camposampiero, University of Padua, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Giacometti
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Facchin
authors.affiliation: Anatomic Pathology Unit, ULSS 15, Alta Padovana, Camposampiero, University of Padua, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Cassaro
authors.affiliation: Gastroenterology Unit, Sant'Antonio Hospital, University of Padua, Italy.
authors.forename: Ennio
authors.initials: E
authors.lastname: Guido
authors.affiliation: Gastroenterology Unit, Sant'Antonio Hospital, University of Padua, Italy.
authors.forename: Franca
authors.initials: F
authors.lastname: De Lazzari
authors.affiliation: Interdepartmental Research Centre for Innovative Biotechnologies (CRIBI), University of Padua, Italy ; Proteomics Facility, Azienda Ospedaliera di Padova, Padua, Italy.
authors.forename: Oriano
authors.initials: O
authors.lastname: Marin
authors.affiliation: Faculty of Chemical and Process Engineering, Warsaw University of Technology, Warsaw, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Ciach
authors.affiliation: CNRS, ITAV-USR 3505, Toulouse, France ; Université de Toulouse, ITAV-USR 3505, Toulouse, France.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Fery-Forgues
authors.affiliation: Department of Molecular Medicine, University of Padua, Padua, Italy ; Venetian Institute of Molecular Medicine, University of Padua, Padua, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Alberti
authors.affiliation: Endoscopy Unit, Veneto Institute of Oncology (IOV-IRCCS), Padua, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Battaglia
authors.affiliation: Endoscopy Unit, Veneto Institute of Oncology (IOV-IRCCS), Padua, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Realdon
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D000595:Amino Acid Sequence; D000818:Animals; D001471:Barrett Esophagus / Q000473:pathology*; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000473:pathology*; D005453:Fluorescence; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal / Q000379:methods*; D008969:Molecular Sequence Data; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D010455:Peptides / Q000737:chemistry; D017207:Rats, Sprague-Dawley; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D010455:Peptides
keywords: Barrett’s esophagus; confocal laser endomicroscopy; diagnostics; esophageal adenocarcinoma; fluorescent nanoparticles; heptapeptide