A potential of peanut agglutinin-immobilized fluorescent nanospheres as a safe candidate of diagnostic drugs for colonoscopy

Sakuma, Shinji; Kataoka, Makoto; Higashino, Haruki; Yokota, Takanori; Masaoka, Yoshie; Yamashita, Shinji; Hiwatari, Ken‐ichiro; Tachikawa, Hiroyuki; Kimura, Ryoji; Nakamura, Kunio; Kumagai, Hironori; Gore, John C.; Pham, Wellington

doi:10.1016/j.ejps.2010.12.011

Cited by 15 publications

(17 citation statements)

References 38 publications

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“…Macromolecules, such as lectins immobilized on the nanosphere surface through chemical reactions with functional groups of polyvinyl chains, confer unique properties that nanospheres do not originally possess [24]. Based on core-corona type nanospheres, we designed a non-absorbable imaging agent that is administered intracolonically and recognizes tumor-derived changes on the mucosal side of large intestinal epithelial cells with high affinity and specificity [25][26][27][28][29].…”

Section: Design Of the Imaging Agentmentioning

confidence: 99%

“…We assessed the safety of the imaging agent [28]. The imaging agent is designed as a non-absorbable diagnostic drug.…”

Section: Safety Of the Imaging Agentmentioning

confidence: 99%

“…Recovery of the Imaging Agent and Coumarin 6 at 2 h After their Incubation in the Closed Colonic Loop (Mean ±s.d., n=3)[28] …”

mentioning

confidence: 99%

“…(8). Assays of ALP ( ) and LDH ( ) in the luminal content of the large intestine after incubation with the respective media[28]. Concentrations of the imaging agent, methyl cellulose, and TritonX-100 were adjusted to 20 mg/mL, and PBS was used as the solvent.…”

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confidence: 99%

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Lectin-Immobilized Fluorescent Nanospheres for Targeting to Colorectal Cancer from a Physicochemical Perspective

Sakuma¹,

Yamashita²,

Hiwatari³

et al. 2011

CDDT

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The goal of this research is to develop an imaging agent that enables real-time and accurate diagnosis of small-sized colorectal cancer. Since colorectal cancer initially develops in the mucous membrane of the large intestine, a nonabsorbable colonoscopic imaging agent capable of being administered intracolonically was designed. The imaging agent is peanut agglutinin (PNA)-immobilized polystyrene nanospheres with surface poly(N-vinylacetamide) (PNVA) chains encapsulating coumarin 6. PNA is a targeting moiety that binds to β-D-galactosyl-(1-3)-N-acetyl-D-galactosamine, which is the terminal sugar of the Thomsen-Friedenreich antigen that is specifically expressed on the mucosal side of colorectal cancer cells. PNVA is immobilized with the aim of reducing nonspecific interactions between the imaging agent and normal tissues, because the initial tumor-derived change is very small throughout the entire large intestine. Coumarin 6 is encapsulated into nanosphere cores to provide endoscopically-detectable fluorescence intensity. It is anticipated that the intracolonically-administered imaging agent recognizes tumor-derived changes in the large intestinal mucosa with high affinity and specificity. Real-time and accurate diagnosis of small-sized early colorectal cancer can be achieved through an imaging agent providing clear fluorescence contrast between normal and cancer tissues observed with a florescence endoscope. This review describes the design concept of this nanoprobe from a physicochemical perspective.

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Section: Design Of the Imaging Agentmentioning

confidence: 99%

“…We assessed the safety of the imaging agent [28]. The imaging agent is designed as a non-absorbable diagnostic drug.…”

Section: Safety Of the Imaging Agentmentioning

confidence: 99%

“…Recovery of the Imaging Agent and Coumarin 6 at 2 h After their Incubation in the Closed Colonic Loop (Mean ±s.d., n=3)[28] …”

mentioning

confidence: 99%

mentioning

confidence: 99%

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Lectin-Immobilized Fluorescent Nanospheres for Targeting to Colorectal Cancer from a Physicochemical Perspective

Sakuma¹,

Yamashita²,

Hiwatari³

et al. 2011

CDDT

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“…16,17 Furthermore, nondegradable fluorescent polystyrene (PS) and poly(methyl methacrylate) NPs have also been investigated successfully offering higher long-term stability for in vitro and in vivo cell imaging. 18,19 In a specific example Landfester reported the synthesis of functional fluorescent polystyrene NPs by miniemulsion polymerization incorporating functional acrylates for colloidal stability and as potential handles for postmodification. Cell uptake was visualized by fluorescent spectroscopy.…”

Section: ■ Introductionmentioning

confidence: 99%

Facile Synthesis of Fluorescent Latex Nanoparticles with Selective Binding Properties Using Amphiphilic Glycosylated Polypeptide Surfactants

et al. 2014

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Specificity of lectin‐immobilized fluorescent nanospheres for colorectal tumors in a mouse model which better resembles the clinical disease

Kitamura

Sakuma

Shimosato

et al. 2014

Contrast Media & Molecular

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We are investigating an imaging agent that enables real-time and accurate diagnosis of early colorectal cancer at the intestinal mucosa by colonoscopy. The imaging agent is peanut agglutinin-immobilized polystyrene nanospheres with surface poly(N-vinylacetamide) chains encapsulating coumarin 6. Intracolonically-administered lectin-immobilized fluorescent nanospheres detect tumor-derived changes through molecular recognition of lectin for the terminal sugar of cancer-specific antigens on the mucosal surface. The focus of this study was to evaluate imaging abilities of the nanospheres in animal models that reflect clinical environments. We previously developed an orthotopic mouse model with human colorectal tumors growing on the mucosa of the descending colon to more resemble the clinical disease. The entire colon of the mice in the exposed abdomen was monitored in real-time with an in vivo imaging apparatus. Fluorescence from the nanospheres was observed along the entire descending colon after intracolonical administration of them from the anus. When the luminal side of the colon was washed with PBS, most of the nanospheres drained away. However, fluorescence persisted in areas where the cancer cells were implanted. Histological evaluation demonstrated that tumors were present in the mucosal epithelia where the nanospheres fluoresced. In contrast, no fluorescence was observed when control mice without tumors were tested. The lectin-immobilized fluorescent nanospheres were tumor specific and bound to tumors even after vigorously washing. The nanospheres non-specifically bound to normal mucosa were easily removed through mild washing. Results indicate that the nanospheres accompanied by colonoscopy will be a clinically-valuable diagnostic tool for the early stage primary colon carcinoma.

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A potential of peanut agglutinin-immobilized fluorescent nanospheres as a safe candidate of diagnostic drugs for colonoscopy

Abstract: SummaryThere is a reasonable likelihood that peanut agglutinin--immobilized fluorescent nanospheres will be developed as a colonoscopic imaging agent from a safety perspective.

Cited by 15 publications

References 38 publications

Lectin-Immobilized Fluorescent Nanospheres for Targeting to Colorectal Cancer from a Physicochemical Perspective

Lectin-Immobilized Fluorescent Nanospheres for Targeting to Colorectal Cancer from a Physicochemical Perspective

Facile Synthesis of Fluorescent Latex Nanoparticles with Selective Binding Properties Using Amphiphilic Glycosylated Polypeptide Surfactants

Specificity of lectin‐immobilized fluorescent nanospheres for colorectal tumors in a mouse model which better resembles the clinical disease

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