Early breast cancer screening using iron/iron oxide-based nanoplatforms with sub-femtomolar limits of detection.
Early breast cancer screening using iron/iron oxide-based nanoplatforms with sub-femtomolar limits of detection.
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DOI：
10.3762/bjnano.7.33
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发表时间：
2016
影响因子：
3.1
通讯作者：
Bossmann SH
中科院分区：
文献类型：
--
作者：
Udukala DN;Wang H;Wendel SO;Malalasekera AP;Samarakoon TN;Yapa AS;Abayaweera G;Basel MT;Maynez P;Ortega R;Toledo Y;Bossmann L;Robinson C;Janik KE;Koper OB;Li P;Motamedi M;Higgins DA;Gadbury G;Zhu G;Troyer DL;Bossmann SH
蛋白酶，包括基质金属蛋白酶（MMP）、组织丝氨酸蛋白酶和组织蛋白酶（CTS），在肿瘤生物学中表现出许多功能。实体瘤的特征在于肿瘤和周围组织的蛋白酶表达水平的变化。因此，监测组织样本和液体活检中的蛋白酶水平是早期癌症检测的重要策略。用于蛋白酶检测的基于水分散性Fe/Fe 3 O 4-核/壳的纳米平台能够检测低至亚飞摩尔检测限的蛋白酶活性。它们的特征在于一种染料（四（羧基苯基）卟啉（TCPP））通过蛋白酶可切割的共有序列和直接连接的第二种染料（Cy 5.5）连接到中心纳米颗粒。基于尿激酶纤溶酶原激活物（uPA）、MMPs 1、2、3、7、9和13以及CTS B和L的蛋白酶活性，可以通过简单的血清试验在I期检测人乳腺癌。通过监视CTS B和L，可以实现阶段0检测。这项由46名乳腺癌患者和20名明显健康的人类受试者组成的初步研究证明了基于蛋白酶活性的液体活检用于早期癌症诊断的可行性。
Proteases, including matrix metalloproteinases (MMPs), tissue serine proteases, and cathepsins (CTS) exhibit numerous functions in tumor biology. Solid tumors are characterized by changes in protease expression levels by tumor and surrounding tissue. Therefore, monitoring protease levels in tissue samples and liquid biopsies is a vital strategy for early cancer detection. Water-dispersable Fe/Fe3O4-core/shell based nanoplatforms for protease detection are capable of detecting protease activity down to sub-femtomolar limits of detection. They feature one dye (tetrakis(carboxyphenyl)porphyrin (TCPP)) that is tethered to the central nanoparticle by means of a protease-cleavable consensus sequence and a second dye (Cy 5.5) that is directly linked. Based on the protease activities of urokinase plasminogen activator (uPA), MMPs 1, 2, 3, 7, 9, and 13, as well as CTS B and L, human breast cancer can be detected at stage I by means of a simple serum test. By monitoring CTS B and L stage 0 detection may be achieved. This initial study, comprised of 46 breast cancer patients and 20 apparently healthy human subjects, demonstrates the feasibility of protease-activity-based liquid biopsies for early cancer diagnosis.