Mouffouk Fouzi, Aouabdi Sihem, Al-Hetlani Entesar, Serrai Hacene, Alrefae Tareq, Leo Chen Liaohai
Department of Chemistry, Kuwait University, Safat, Kuwait.
King Abdullah International Medical Research Center (KAIMRC), Jeddah, Kingdom of Saudi Arabia.
Int J Nanomedicine. 2017 Apr 13;12:3037-3047. doi: 10.2147/IJN.S127086. eCollection 2017.
Screening and early diagnosis are the key factors for the reduction of mortality rate and treatment cost of cancer. Therefore, sensitive and selective methods that can reveal the low abundance of cancer biomarkers in a biological sample are always desired. Here, we report the development of a novel electrochemical biosensor for early detection of breast cancer by using bioconjugated self-assembled pH-responsive polymeric micelles. The micelles were loaded with ferrocene molecules as "tracers" to specifically target cell surface-associated epithelial mucin (MUC1), a biomarker for breast and other solid carcinoma. The synthesis of target-specific, ferrocene-loaded polymeric micelles was confirmed, and the resulting sensor was capable of detecting the presence of MUC1 in a sample containing about 10 cells/mL. Such a high sensitivity was achieved by maximizing the loading capacity of ferrocene inside the polymeric micelles. Every single event of binding between the antibody and antigen was represented by the signal of hundreds of thousands of ferrocene molecules that were released from the polymeric micelles. This resulted in a significant increase in the intensity of the ferrocene signal detected by cyclic voltammetry.
筛查和早期诊断是降低癌症死亡率和治疗成本的关键因素。因此，人们一直渴望有灵敏且具选择性的方法，能够揭示生物样本中低丰度的癌症生物标志物。在此，我们报告了一种新型电化学生物传感器的研发，该传感器利用生物共轭的自组装pH响应聚合物胶束用于早期检测乳腺癌。胶束中装载了二茂铁分子作为“示踪剂”，以特异性靶向细胞表面相关上皮粘蛋白（MUC1），这是乳腺癌和其他实体癌的一种生物标志物。确认了靶向特异性、装载二茂铁的聚合物胶束的合成，所得传感器能够检测含有约10个细胞/毫升的样本中MUC1的存在。通过最大化聚合物胶束中二茂铁的负载量实现了如此高的灵敏度。抗体与抗原之间的每一次结合事件都由从聚合物胶束中释放的数十万二茂铁分子的信号表示。这导致循环伏安法检测到的二茂铁信号强度显著增加。
