Tumor recognition of peanut agglutinin-immobilized fluorescent nanospheres in biopsied human tissues.
Biomarker imaging
Colorectal cancer
Diagnostic agent
Nanosphere
Optical imaging
Peanut agglutinin
Thomsen-Friedenreich antigen
Journal
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
ISSN: 1873-3441
Titre abrégé: Eur J Pharm Biopharm
Pays: Netherlands
ID NLM: 9109778
Informations de publication
Date de publication:
Mar 2019
Mar 2019
Historique:
received:
20
07
2018
revised:
21
12
2018
accepted:
08
01
2019
pubmed:
15
1
2019
medline:
31
5
2019
entrez:
15
1
2019
Statut:
ppublish
Résumé
We are investigating an imaging agent for early detection of colorectal cancer. The agent, named the nanobeacon, is coumarin 6-encapsulated polystyrene nanospheres whose surfaces are covered with poly(N-vinylacetamide) and peanut agglutinin that reduces non-specific interactions with the normal mucosa and exhibits high affinity for terminal sugars of the Thomsen-Friedenreich antigen, which is expressed cancer-specifically on the mucosa, respectively. We expect that cancer can be diagnosed by detecting illumination of intracolonically administered nanobeacon on the mucosal surface. In the present study, biopsied human tissues were used to evaluate the potential use of the nanobeacon in the clinic. Prior to the clinical study, diagnostic capabilities of the nanobeacon for detection of colorectal cancer were validated using 20 production batches whose characteristics were fine-tuned chemically for the purpose. Ex vivo imaging studies on 66 normal and 69 cancer tissues removed from the colons of normal and orthotopic mouse models of human colorectal cancer, respectively, demonstrated that the nanobeacon detected colorectal cancer with excellent capabilities whose rates of true and false positives were 91% and 5%, respectively. In the clinical study, normal and tumor tissues on the large intestinal mucosa were biopsied endoscopically from 11 patients with colorectal tumors. Histological evaluation revealed that 9 patients suffered from cancer and the rest had adenoma. Mean fluorescence intensities of tumor tissues treated with the nanobeacon were significantly higher than those of the corresponding normal tissues. Correlation of magnitude relation of the intensity in individuals was observed in cancer patients with a high probability (89%); however, the probability reduced to 50% in adenoma patients. There was a reasonable likelihood for diagnosis of colorectal cancer by the nanobeacon applied to the mucosa of the large intestine.
Identifiants
pubmed: 30639308
pii: S0939-6411(18)30883-X
doi: 10.1016/j.ejpb.2019.01.007
pmc: PMC6456895
mid: NIHMS1518687
pii:
doi:
Substances chimiques
Coumarins
0
Fluorescent Dyes
0
Peanut Agglutinin
0
Thiazoles
0
coumarin 6
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
29-37Subventions
Organisme : NCI NIH HHS
ID : R01 CA160700
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier B.V. All rights reserved.
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