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.

Molecular endoscopic imaging in cancer

“…An important in vivo study combining organic NP (nanoparticle) and CLE for highlighting esophageal cancer conditions was carried out where NP conjugated with peptides (ASYNYDA) specific for human and rat esophageal cancer cells and loaded with fluorescent dye [4‐(dicyanomethylene)‐2‐methyl‐6‐(4‐dimethylaminostyryl)‐4H‐pyran] (DCM) were i.v. injected and fluorescence was observed in rats affected by esophageal cancer, whereas no signal was observed in control . The study confirmed that nanoparticles could serve as a potential cancer diagnostic tool.…”

“…injected and fluorescence was observed in rats affected by esophageal cancer, whereas no signal was observed in control. 43 The study confirmed that nanoparticles could serve as a potential cancer diagnostic tool.…”

Conjugates of Benzoxazole and GFP Chromophore with Aggregation‐Induced Enhanced Emission: Influence of the Chain Length on the Formation of Particles and on the Dye Uptake by Living Cells

“…The incorporation of NPs was not observed, whatever the compound. Since the red fluorescence signal arising from NPs was much more stable under the microscope laser beam than the blue signal arising from the dispersed dyes, it could be interesting to modify the NP surface to promote cell uptake . This could allow bioimaging experiments over a long period of time.…”

Hyperinsulinemia Promotes Esophageal Cancer Development in a Surgically-Induced Duodeno-Esophageal Reflux Murine Model

“…At 13 weeks of age, 39 WT ( n = 20 females, n = 19 males) and 40 MKR ( n = 20 females, n = 20 males) mice underwent jejunum-esophageal anastomosis. The operation to induce chronic duodeno-esophageal reflux was performed according to the microsurgical procedure described in our previous studies [ 43 , 44 ] with some modification. Briefly, following induction of anesthesia with intraperitoneal injection (tiletamine/zolazepam (25 mg/Kg) and xylazine (2 mg/Kg)), a 2-cm midline laparotomy incision was made.…”