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成像剂，可以识别大肠粘膜中肿瘤的变化。该试剂由钢琴凝集素（PNA）弹性聚苯乙烯纳米球组成p-d-半乳糖基（1-3）-N-乙酰基-D-半乳糖胺（GAL-β（1-3）CRA1NAC），它是特异性在大肠癌细胞的粘液侧表达的Thomsen-Friedenreich（TF）抗原的末端糖。预计PNVA可以通过减少成像剂与正常组织之间的非特异性相互作用来增强PNA对碳水化合物残留物的特异性。香豆素6被预期提供可检测到可检测的荧光强度，通过其串联的疏水相互作用将纳米球的聚苯乙烯核包裹在聚苯乙烯核心中。 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提高了PNA的特异性，如我们预期的那样。对成像剂与各种培养的人类细胞之间相互作用的体外研究表明，通过识别Cral-β（1-3）GA1NAC，这是抗原的末端糖，与具有高亲和力和特异性的表达TF抗原癌细胞结合的成像剂。我们只是在检查成像剂在含有肿瘤动物模型中的有用性。在大肿瘤小鼠的大肠粘膜中观察到了源自成像剂的荧光的定位，但是未观察到正常小鼠的大肠粘膜中明显的荧光。初步体内数据表明，可以通过观察荧光内窥镜正常和癌性尖端之间的清晰荧光对比来检测有色癌。有关体内研究的详细信息将来会描述。较少的

项目成果

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

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

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;Kiyoko Iwata
• 通讯作者: Kiyoko Iwata