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

我们设计了一种新型结肠镜显像剂，可以识别大肠粘膜肿瘤源性变化。该制剂由花生凝集素(PNA)-固定化聚苯乙烯纳米球组成，表面聚n -乙烯乙酰胺（PNVA）链包封荧光香豆素6。PNA是结合p - d -半乳糖基-(1-3)- n-乙酰基- d -半乳糖胺（Gal-β(1-3)Cra1NAc）的靶向片段，Gal-β(1-3)Cra1NAc是thomson - friedenreich （TF）抗原的末端糖，在结直肠癌细胞的粘膜侧特异性表达。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增强PNA对碳水化合物残基的特异性。香豆素6有望提供内窥镜可检测的荧光强度，通过其串状疏水相互作用被封装在纳米球的聚苯乙烯内核中。在PNA免疫作用下，正常红细胞和表达Gal- 1-3 galnac的红细胞被凝集，更多具有表面PNVA链的荧光纳米球（显像剂）显示，PNA被主动固定在纳米球表面，对Gal-β(1-3)CralNAc具有很强的亲和力，与完整的PNA相当，PNVA增强了PNA对碳水化合物残留物的特异性，正如我们所期望的那样。体外显像剂与各种培养的人类细胞相互作用的研究表明，显像剂通过识别抗原的末端糖Cral-β(1-3)Ga1NAc，以高亲和力和特异性结合表达TF抗原的癌细胞。我们只是在检查显像剂在荷瘤动物模型中的有用性。显像剂产生的荧光在荷瘤小鼠的大肠黏膜中有定位，而在正常小鼠的大肠黏膜中没有明显的荧光。初步的体内数据表明，在荧光内窥镜下，通过观察正常组织和癌组织之间清晰的荧光对比，可以检测出结直肠癌。关于体内研究的细节将在将来描述。少

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