The Institute of Nanotechnology and Advanced Materials, Department of Chemistry, Bar-Ilan University, Ramat-Gan 52900, Israel.
J Nanobiotechnology. 2012 Aug 14;10:36. doi: 10.1186/1477-3155-10-36.
The use of near-infrared (NIR) fluorescence imaging techniques has gained great interest for early detection of cancer because water and other intrinsic biomolecules display negligible absorption or autofluorescence in this region. Novel fluorescent nanoparticles with potential to improve neoplasm detection sensitivity may prove to be a valuable tool in early detection of colon tumors.
The present study describes the synthesis and use of NIR fluorescent albumin nanoparticles as a diagnostic tool for detection of colon cancer. These fluorescent nanoparticles were prepared by a precipitation process of human serum albumin (HSA) in aqueous solution in the presence of a carboxylic acid derivative of the NIR dye IR-783 (CANIR). Tumor-targeting ligands such as peanut agglutinin (PNA), anti-carcinoembryonic antigen antibodies (anti-CEA) and tumor associated glycoprotein-72 monoclonal antibodies (anti-TAG-72) were covalently conjugated to the albumin nanoparticles via the surface carboxylate groups by using the carbodiimide activation method.
Leakage of the encapsulated dye into PBS containing 4% HSA or human bowel juice was not detected. This study also demonstrates that the encapsulation of the NIR fluorescent dye within the HSA nanoparticles reduces the photobleaching of the dye significantly. Specific colon tumor detection in a mouse model was demonstrated for PNA, anti-CEA and anti-TAG-72 conjugated NIR fluorescent HSA nanoparticles. These bioactive NIR fluorescent albumin nanoparticles also detected invisible tumors that were revealed as pathological only subsequent to histological analysis.
These results may suggest a significant advantage of NIR fluorescence imaging using NIR fluorescent nanoparticles over regular colonoscopy. In future work we plan to broaden this study by encapsulating cancer drugs, such as paclitaxel and doxorubicin, within these biodegradable NIR fluorescent HSA nanoparticles, in order to use them for both detection as well as therapy of colon cancer and others.
近红外（NIR）荧光成像技术因其在该区域内水和其他内源性生物分子几乎没有吸收或自发荧光而受到极大关注，可用于癌症的早期检测。具有提高肿瘤检测灵敏度潜力的新型荧光纳米粒子可能成为早期检测结肠癌的有用工具。
本研究描述了 NIR 荧光白蛋白纳米粒子作为结肠癌检测诊断工具的合成和应用。这些荧光纳米粒子是通过在水相中白蛋白（HSA）的沉淀过程中制备的，其中存在 NIR 染料 IR-783（CANIR）的羧酸衍生物。肿瘤靶向配体，如花生凝集素（PNA）、癌胚抗原抗体（抗-CEA）和肿瘤相关糖蛋白-72 单克隆抗体（抗-TAG-72），通过碳二亚胺活化法通过表面羧酸盐基团共价连接到白蛋白纳米粒子上。
未检测到包封染料向含有 4%HSA 或人肠液的 PBS 中的泄漏。本研究还表明，将 NIR 荧光染料包封在 HSA 纳米粒子内可显著减少染料的光漂白。PNA、抗-CEA 和抗-TAG-72 偶联的 NIR 荧光 HSA 纳米粒子在小鼠模型中证明了对结肠癌的特异性检测。这些生物活性 NIR 荧光白蛋白纳米粒子还检测到了仅在组织学分析后才显示为病理性的不可见肿瘤。
这些结果可能表明使用 NIR 荧光纳米粒子进行 NIR 荧光成像具有明显优于常规结肠镜检查的优势。在未来的工作中，我们计划在这些可生物降解的 NIR 荧光 HSA 纳米粒子中封装癌症药物，如紫杉醇和阿霉素，以将其用于结肠癌和其他癌症的检测和治疗。
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