Essence of affinity and specificity of peanut agglutinin-immobilized fluorescent nanospheres with surface poly(N-vinylacetamide) chains for colorectal cancer

• Published in: European journal of pharmaceutics and biopharmaceutics Vol. 79; no. 3; pp. 537 - 543
• Main Authors: Sakuma, Shinji, Higashino, Haruki, Oshitani, Hitomi, Masaoka, Yoshie, Kataoka, Makoto, Yamashita, Shinji, Hiwatari, Ken-ichiro, Tachikawa, Hiroyuki, Kimura, Ryoji, Nakamura, Kunio, Kumagai, Hironori, Gore, John C., Pham, Wellington
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.11.2011; Elsevier
• Subjects: Acetamides - chemistry; Animals; Antigens, Tumor-Associated, Carbohydrate - metabolism; Biological and medical sciences; Cecum - metabolism; Cecum - pathology; Chemistry, Pharmaceutical; Colonoscopy; Colorectal cancer; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Contrast Media - chemistry; Endoscopic imaging agent; Female; Fluorescent Dyes - chemistry; General pharmacology; HT29 Cells; Humans; Imaging; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; Medical sciences; Mice; Mice, SCID; Microscopy, Fluorescence; Nanospheres - chemistry; Neoplasm Transplantation; Peanut agglutinin; Peanut Agglutinin - chemistry; Peanut Agglutinin - metabolism; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Poly(N-vinylacetamide); Polyvinyls - chemistry; Surface Properties; Peanut agglutinin; Endoscopic imaging agent; Poly(N-vinylacetamide); Imaging; Colonoscopy; Colorectal cancer; Rectal disease; Pharmaceutical technology; Immobilization; Malignant tumor; Colonic disease; Specificity; Agglutinin; Digestive diseases; Intestinal disease; Affinity; Medical imagery; Nanosphere; Cancer
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2011.06.001

Peanut agglutinin (PNA) and poly(N-vinylacetamide) (PNVA) were essential for biorecognition for tumor tissues and a reduction of nonspecific interactions with normal tissues, respectively. 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.