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

我们设计了一种新的结肠镜成像剂，可以识别大肠粘膜中的肿瘤源性变化。该试剂由花生凝集素（PNA）固定的聚苯乙烯纳米球与表面聚（N-乙烯基乙酰胺）（PNVA）链封装荧光香豆素6。PNA是结合β-D-半乳糖基-（1-3）-N-乙酰基-D-半乳糖胺（Gal-β（1-3）Cra 1 NAc）的靶向部分，Gal-β（1-3）Cra 1 NAc是在结肠直肠癌细胞的粘膜侧特异性表达的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增强PNA对碳水化合物残基的特异性。香豆素6，这是预期提供内窥镜可检测的荧光强度，封装到聚苯乙烯核的纳米球通过其串的疏水相互作用。存在PNA免疫时正常和Gal-（1-3）GalNAc表达红细胞的凝集 ...更多信息 与PNVA链结合的荧光纳米球（显像剂）显示PNA被主动固定在纳米球表面，其对Gal-β（1-3）CralNAc的亲和力与完整PNA相当，并且PNVA增强了PNA对糖残基的特异性。在体外研究中，显像剂与各种培养的人细胞之间的相互作用表明，显像剂通过识别抗原的末端糖Cral-β（1-3）Ga 1 NAc，以高亲和力和特异性结合表达TF抗原的癌细胞。我们只是在研究显像剂在荷瘤动物模型中的作用。在荷瘤小鼠的大肠粘膜中观察到来自显像剂的荧光的定位，但在正常小鼠的大肠粘膜中未观察到显著的荧光。初步的体内数据表明，结直肠癌可以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来检测。有关体内研究的详细信息将在以后描述。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