Study on diagnosis and treatment of cancer in the gastrointestine using cancer-recognizable nanocarriers

利用癌症识别纳米载体诊断和治疗胃肠道癌症的研究

• 批准号: 18590160
• 负责人: SAKUMA Shinji
• 金额: $ 2.51万
• 依托单位: Setsunan University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590160/
• 关键词: Colorectal cancer; Endoscopy; Imaging agent; Lectin; Nanomedicine

We designed a novel colonoscopic imaging agent that can recognize tumor-derived changes in the large intestinal mucosa. The agent was composed of peanut agglutinin (PNA)-immobilized polystyrene nanospheres with surface poly(N-vinylacetamide) (PNVA) chains encapsulating fluorescent coumarin 6. PNA was a targeting moiety that binds to P-D-galactosyl-(1-3)-N-acetyl-D-galactosamine(Gal-β(1-3)Cra1NAc), which is the terminal sugar of the Thomsen-Friedenreich (TF) antigen that is specifically expressed on the mucasal side of colorectal cancer cells. PNVA was expected to enhance the specificity of PNA for the carbohydrate residues by reducing nonspecific interactions between imaging agents and normal tissues. Coumarin 6, which was expected to provide endoscopically detectable fluorescence intensity, was encapsulated into polystyrene cores of nanospheres through their strung hydrophobic interactions. Agglutination of normal and Gal-(1-3)GalNAc-expressing erythrocytes in the presence of PNA-immo … More bilized fluorescent nanospheres with surface PNVA chains (imaging agents) showed that PNA was actively immobilized on the nanosphere surface with a strong affinity for Gal-β(1-3)CralNAc, which was equivalent to that of intact PNA, and that PNVA enhanced the specificity of PNA for the carbohydrate residue as we expected. In vitro studies on interactions between imaging agents and various cultured human cells indicated that imaging agents bound to the TF antigen-expressing cancer cells with high affinity and specificity by recognizing Cral-β(1-3)Ga1NAc which is the terminal sugar of the antigen. We are just examining the usefulness of imaging agents in tumor-bearing animal models. The localization of fluorescence derived from imaging agents was observed in the large intestinal mucosa of tumor-bearing mice, but significant fluorescence in the large intestinal mucosa of normal mice was not observed. Preliminary in vivo data suggest that colorectal cancer can be detected by observing a clear fluorescent contrast between normal and cancerous tissues under a fluorescent endoscope. Details concerning in vivo studies will be described in future. Less

我们设计了一种新型的结肠镜显像剂，可以识别大肠粘膜中肿瘤衍生的变化。该试剂由花生凝集素(PNA)固定的聚苯乙烯纳米球和包裹荧光香豆素6的表面聚N-乙烯基乙酰胺(PNVA)链组成。花生凝集素是一种靶向部分，与P-D-galactosyl-(1-3)-N-acetyl-D-galactosamine(Gal-β(1-3)Cra1NAc)，结合，Tf是结直肠癌细胞粘液侧特异表达的汤姆森-弗里登瑞克(TF)抗原的末端糖。PNVA有望通过减少显像剂与正常组织之间的非特异性相互作用来提高PNA对碳水化合物残基的特异性。香豆素6有望提供内窥镜下可检测到的荧光强度，通过其强烈的疏水相互作用被包裹到聚苯乙烯纳米球的核心中。PNA-免疫…对正常和表达Gal-(1-3)GalNAc的红细胞的凝集作用更多的带有表面PNVA链的荧光纳米球(显像剂)表明，PNA被活性地固定在纳米球表面，与Gal-β(1-3)CralNAc具有很强的亲和力，与完整的PNA相当，PNVA如我们预期的那样提高了PNA对碳水化合物残基的特异性。体外对显像剂与多种培养的人细胞相互作用的研究表明，显像剂通过识别Tf抗原的末端糖CRAL-β(1-3)Ga1NAc与表达Tf抗原的癌细胞结合，具有很高的亲和力和特异性。我们只是在检查显像剂在荷瘤动物模型中的实用性。在荷瘤小鼠的大肠粘膜中观察到显像剂衍生的荧光的定位，而在正常小鼠的大肠粘膜中未观察到明显的荧光。初步的活体数据表明，通过在荧光内窥镜下观察正常组织和癌组织之间的清晰荧光对比，可以检测到结直肠癌。关于体内研究的细节将在未来描述。较少

项目成果

Lectin-immobilized fluorescent nanocarrier with surface poly(N-vinylacetamide) chains as an endoscopic imaging agent

具有表面聚（N-乙烯基乙酰胺）链的凝集素固定荧光纳米载体作为内窥镜成像剂

• 发表时间: 2006
• 作者: Sakabe M;Matsui H;Sakata H;Ikeda K;Yamagishi T;Nakajima Y.;佐久間 信至;Shinji Sakuma;日渡 謙一郎;Ken-ichiro Hiwatari;Ken-ichiro Hiwatari;Ken-ichiro Hiwatari;佐久間 信至;Shinji Sakuma;Kiyoko Iwata;Kiyoko Iwata;Kiyoko Iwata;Kiyoko Iwata;岩田 記代子;Kiyoko Iwata;岩田 記代子;Kiyoko Iwata;Shinji Sakuma;Shinji Sakuma;Ken-ichiro Hiwatari;Ken-ichiro Hiwatari
• 通讯作者: Ken-ichiro Hiwatari

Lectin-immobilized fluorescent nanospheres with surface poly(N-vinylacetamide)(PNVA) chains as colonoscopic imaging agents-Effect of molecular weight of PNVA on lectin-induced biorecognition-

具有表面聚（N-乙烯基乙酰胺）（PNVA）链的凝集素固定荧光纳米球作为结肠镜成像剂-PNVA分子量对凝集素诱导的生物识别的影响-

• 发表时间: 2007
• 作者: Sakabe M;Matsui H;Sakata H;Ikeda K;Yamagishi T;Nakajima Y.;佐久間 信至;Shinji Sakuma;日渡 謙一郎;Ken-ichiro Hiwatari;Ken-ichiro Hiwatari;Ken-ichiro Hiwatari
• 通讯作者: Ken-ichiro Hiwatari

Use of endoscopic fluorescent nanocarriers with targeting moieties for the diagnosis of early colorectal cancer-Poly(N-vinylacetamide)immobilized on the nanocarrier surface reduces non-specific interactions between nanocarriers and cells-

使用带有靶向部分的内窥镜荧光纳米载体诊断早期结直肠癌-固定在纳米载体表面的聚（N-乙烯基乙酰胺）减少了纳米载体与细胞之间的非特异性相互作用-

• 发表时间: 2006
• 作者: Sakabe M;Matsui H;Sakata H;Ikeda K;Yamagishi T;Nakajima Y.;佐久間 信至;Shinji Sakuma;日渡 謙一郎;Ken-ichiro Hiwatari;Ken-ichiro Hiwatari;Ken-ichiro Hiwatari;佐久間 信至;Shinji Sakuma;Kiyoko Iwata
• 通讯作者: Kiyoko Iwata

消化器癌認識佐ナノキャリアを用いたナノ診断・治療システムの構築-ナノキャリアの設計・合成及びin vitro機能性評価-

构建利用纳米载体识别胃肠道癌症的纳米诊断和治疗系统 - 纳米载体的设计与合成及体外功能评价 -

• 发表时间: 2006
• 作者: Sakabe M;Matsui H;Sakata H;Ikeda K;Yamagishi T;Nakajima Y.;佐久間 信至;Shinji Sakuma;日渡 謙一郎;Ken-ichiro Hiwatari;Ken-ichiro Hiwatari;Ken-ichiro Hiwatari;佐久間 信至;Shinji Sakuma;Kiyoko Iwata;Kiyoko Iwata;Kiyoko Iwata;Kiyoko Iwata;岩田 記代子;Kiyoko Iwata;岩田 記代子
• 通讯作者: 岩田 記代子

Peanut agglutinin-immobilized fluorescent nanocarrier with surface poly(N-vinylacetamide)chains as an endoscopic imaging agent for the diagnosis of early colorectal cancer

具有表面聚（N-乙烯基乙酰胺）链的花生凝集素固定荧光纳米载体作为内窥镜成像剂用于诊断早期结直肠癌

• 发表时间: 2006
• 作者: Sakabe M;Matsui H;Sakata H;Ikeda K;Yamagishi T;Nakajima Y.;佐久間 信至;Shinji Sakuma;日渡 謙一郎;Ken-ichiro Hiwatari;Ken-ichiro Hiwatari;Ken-ichiro Hiwatari;佐久間 信至;Shinji Sakuma;Kiyoko Iwata;Kiyoko Iwata;Kiyoko Iwata
• 通讯作者: Kiyoko Iwata