基于纳米酶阵列修饰多元掺杂石墨烯纤维微电极的癌细胞电分析体系研究

The level of reactive oxygen species in cancer cells is of important significance to cancer diagnosis and assessment. With recent progresses in nanotechnology and electroanalysis, we propose the development of a high-performance microelectrode for ultrasensitive detection of reactive oxygen species (i.e., H2O2) in live cancer cell samples. In this project, we design the systematic research framework of “function orientation-technology development-structure tuning-performance optimization-application exploitation”. First, the graphene nanosheets will be orderly assembled into microscopic fiber structure. By doping graphene with heteroatoms via novel green strategy, the heteroatom-doped graphene fiber materials will be obtained, which possess unique micro/nano-structures, electronic structure and high chemical activity. Second, the nanoenzyme array with different dimension, morphology and component will be loaded on graphene fiber by highly controllable methods. Taking the advantages of the synergetic contribution from the multi-scale, multi-dimension and multi-component coupling, the overall performance of the resultant nanoenzyme array modified multi-doped graphene fiber microelectrode will be improved to a great extent. Finally, the electrochemical sensor system based on the nanohybrid fiber microelectrode will be established, which can be used for real-time tracking H2O2 secreted from different live cancer cells in normal state/upon being stimulated, and after being treated with radiotherapy and chemotherapy. This could be potentially useful in distinguishing different types of cancer cells, as well as evaluating the pharmacokinetics and therapeutic efficacy in the treatment of cancer. It can be envisioned that this proposal will provide new insights on the design and fabrication of new types of nanohybrid microelectrodes, which will also contribute to developing the cross subjects of electroanalytical chemistry, material science and biomedicine.

癌细胞体系活性氧水平对于癌症诊断和病情评估具有重要价值。本项目以研制用于超灵敏检测癌细胞样品中活性氧类物质H2O2的高性能电极为目标，结合纳米技术和电分析方法的优势，设计“功能导向-技术开发-结构调控-性能优化-应用开拓”的研究体系：开发石墨烯纳米片有序组装成型技术，以及异质原子掺杂石墨烯的绿色工艺，合成具有特殊微纳结构、电子结构和化学活性的多元共掺杂石墨烯宏观纤维材料；设计纳米尺度下以石墨烯纤维为载体负载不同维度、形貌和组成的纳米酶阵列高效可控方法。通过多尺度、多维度、多组分耦合提高纳米酶阵列修饰多元掺杂石墨烯纤维微电极的综合性能，建立用于实时监测不同癌细胞在正常状态/应激状态以及接受放疗或化疗后释放H2O2过程的新型电化学传感系统，为癌细胞的种类鉴定和疗效评估提供有效的电分析方法，为纳米复合微电极的设计和构筑提供全新的思路，促进电分析化学与材料科学、生物医学交叉融合和共同发展。

癌症是严重威胁人类健康的一大类疾病，研发细胞体系小分子代谢物活性氧超灵敏检测技术，对于癌症早期诊断和疗效评估有着重要意义。本项目以研制用于超灵敏检测癌细胞样品中活性氧的高性能电极为目标，开发了石墨烯纳米片有序组装成型技术，以及异质原子掺杂石墨烯的绿色工艺，合成了具有特殊微纳结构、电子结构和化学活性的多元共掺杂石墨烯宏观纤维材料；以多元掺杂石墨烯纤维为载体，采用高效电沉积法和水热沉淀法等在石墨烯纤维上直接生长高度有序的仿生纳米阵列和纳米酶，制得了纳米酶阵列修饰多元掺杂石墨烯纤维微电极，表征了电极的微纳结构并研究了其电化学传感性能。结果表明，电极具有良好的机械强度和生物相容性，检测H2O2时灵敏度高、检测限低、线性范围宽、抗干扰能力强、稳定性和重现性好，能检测癌细胞包括不同类型的乳腺癌细胞和直肠癌细胞等在正常状态/应激状态以及接受化疗药物顺铂治疗后释放H2O2水平，用于鉴别癌细胞和正常细胞、区分不同类型的癌细胞、评估化疗药物对癌细胞活性的影响，为癌症的早期诊断及疗效评估提供了创新的电分析方法。此外微电极还可以插入临床手术切除的肿瘤组织和动物模型组织内，用于检测肿瘤组织中的癌细胞释放的活性氧。面向临床实际应用需要，本项目以柔性石墨烯纳米复合纤维微电极作为植入式电化学传感探针、嵌入微流控芯片中构建了多种不同功能型电化学传感微芯片等实用化器件，开辟了电分析化学和新型功能纳米材料在生物医学领域的应用。在本项目资助下，项目负责人取得一系列研究成果，作为通讯作者发表标注基金号的SCI论文16篇，其中中科院分区一区论文12篇，荣获2020年湖北省自然科学二等奖等。