Engineering of near IR fluorescent albumin nanoparticles for in vivo detection of colon cancer.

Engineering of near IR fluorescent albumin nanoparticles for in vivo detection of colon cancer.
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DOI:
10.1186/1477-3155-10-36
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发表时间:
2012-08-14
影响因子:
10.2
通讯作者:
Margel S
Margel S
中科院分区:
工程技术1区
文献类型:
--
作者:
Cohen S;Margel S

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近红外(NIR)荧光成像技术的使用对于癌症的早期检测已经获得了极大的兴趣,因为水和其他内在生物分子在该区域中显示出可忽略的吸收或自发荧光。具有提高肿瘤检测灵敏度潜力的新型荧光纳米颗粒可能被证明是早期检测结肠肿瘤的有价值的工具。本研究描述了近红外荧光白蛋白纳米颗粒的合成和使用,作为结肠癌检测的诊断工具。这些荧光纳米颗粒通过在NIR染料IR-783(CANIR)的羧酸衍生物存在下在水溶液中的人血清白蛋白(HSA)的沉淀过程来制备。通过碳二亚胺活化法将肿瘤靶向配体如花生凝集素(PNA)、抗癌胚抗原抗体(anti-CEA)和肿瘤相关糖蛋白-72单克隆抗体(anti-TAG-72)通过表面羧酸基团共价结合到白蛋白纳米粒上。未检测到包封染料泄漏到含有4%HSA或人肠液的PBS中。该研究还表明,在HSA纳米颗粒内封装NIR荧光染料显著降低了染料的光漂白。针对PNA、抗CEA和抗TAG-72缀合的NIR荧光HSA纳米颗粒证明了小鼠模型中的特异性结肠肿瘤检测。这些生物活性的NIR荧光白蛋白纳米颗粒还检测了仅在组织学分析之后才被揭示为病理学的不可见肿瘤。这些结果可能表明使用NIR荧光纳米颗粒的NIR荧光成像相对于常规结肠镜检查的显著优势。在未来的工作中,我们计划通过在这些可生物降解的NIR荧光HSA纳米颗粒中封装癌症药物(如紫杉醇和多柔比星)来扩大这项研究,以便将它们用于结肠癌和其他癌症的检测和治疗。
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.
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