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Essence of affinity and specificity of peanut agglutinin-immobilized fluorescent nanospheres with surface poly(N-vinylacetamide) chains for colorectal cancer.
- Source :
-
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V [Eur J Pharm Biopharm] 2011 Nov; Vol. 79 (3), pp. 537-43. Date of Electronic Publication: 2011 Jun 13. - Publication Year :
- 2011
-
Abstract
- We have designed a novel colonoscopic imaging agent that is composed of submicron-sized fluorescent polystyrene nanospheres with two functional groups - peanut agglutinin (PNA) and poly(N-vinylaceamide) (PNVA) - on their surfaces. PNA is a targeting moiety that binds to β-d-galactosyl-(1-3)-N-acetyl-d-galactosamine (Gal-β(1-3)GalNAc), which is the terminal sugar of the Thomsen-Friedenreich antigen that is specifically expressed on the mucosal side of colorectal cancer cells; it is anchored on the nanosphere surface via a poly(methacrylic) acid (PMAA) linker. PNVA is immobilized to enhance the specificity of PNA by reducing nonspecific interactions between the imaging agent and normal tissues. The essential nature of both functional groups was evaluated through in vivo experiments using PNA-free and PNVA-free nanospheres. The imaging agent recognized specifically tumors on the cecal mucosa of immune-deficient mice in which human colorectal cancer cells had been implanted; however, the recognition capability disappeared when PNA was replaced with wheat germ agglutinin, which has no affinity for Gal-β(1-3)GalNAc. PNA-free nanospheres with exclusively surface PNVA chains rarely adhered to the cecal mucosa of normal mice that did not undergo the cancer cell implantation. In contrast, there were strong nonspecific interactions between normal tissues and PNA-free nanospheres with exclusively surface PMAA chains. In vivo data proved that PNA and PNVA were essential for biorecognition for tumor tissues and a reduction of nonspecific interactions with normal tissues, respectively.<br /> (Copyright © 2011 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Antigens, Tumor-Associated, Carbohydrate metabolism
Cecum metabolism
Cecum pathology
Chemistry, Pharmaceutical
Colonoscopy
Colorectal Neoplasms metabolism
Female
HT29 Cells
Humans
Intestinal Mucosa metabolism
Intestinal Mucosa pathology
Mice
Mice, SCID
Microscopy, Fluorescence
Neoplasm Transplantation
Peanut Agglutinin metabolism
Surface Properties
Acetamides chemistry
Colorectal Neoplasms pathology
Contrast Media chemistry
Fluorescent Dyes chemistry
Nanospheres chemistry
Peanut Agglutinin chemistry
Polyvinyls chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3441
- Volume :
- 79
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
- Publication Type :
- Academic Journal
- Accession number :
- 21693188
- Full Text :
- https://doi.org/10.1016/j.ejpb.2011.06.001