title: Essence of affinity and specificity of peanut agglutinin-immobilized fluorescent nanospheres with surface poly(N-vinylacetamide) chains for colorectal cancer.
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.
authors.affiliation: Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, Japan. sakuma@pharm.setsunan.ac.jp
authors.forename: Shinji
authors.initials: S
authors.lastname: Sakuma
authors.forename: Haruki
authors.initials: H
authors.lastname: Higashino
authors.forename: Hitomi
authors.initials: H
authors.lastname: Oshitani
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Masaoka
authors.forename: Makoto
authors.initials: M
authors.lastname: Kataoka
authors.forename: Shinji
authors.initials: S
authors.lastname: Yamashita
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Hiwatari
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tachikawa
authors.forename: Ryoji
authors.initials: R
authors.lastname: Kimura
authors.forename: Kunio
authors.initials: K
authors.lastname: Nakamura
authors.forename: Hironori
authors.initials: H
authors.lastname: Kumagai
authors.forename: John C
authors.initials: JC
authors.lastname: Gore
authors.forename: Wellington
authors.initials: W
authors.lastname: Pham
mesh_terms: D000081:Acetamides / Q000737:chemistry*; D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000378:metabolism; D002432:Cecum / Q000378:metabolism / Q000473:pathology; D002626:Chemistry, Pharmaceutical; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D003287:Contrast Media / Q000737:chemistry*; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry*; D019073:HT29 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D008856:Microscopy, Fluorescence; D054118:Nanospheres / Q000737:chemistry*; D009368:Neoplasm Transplantation; D019887:Peanut Agglutinin / Q000737:chemistry* / Q000378:metabolism; D011145:Polyvinyls / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D000081:Acetamides; D015295:Antigens, Tumor-Associated, Carbohydrate; D003287:Contrast Media; D005456:Fluorescent Dyes; D019887:Peanut Agglutinin; D011145:Polyvinyls; C539745:poly(N-vinylacetamide); C016467:Thomsen-Friedenreich antigen