Biosensors for the programmed cell death (apoptosis)

细胞凋亡在人类疾病及其临床治疗中具有重要意义。未能调控细胞凋亡是包括神经退行性疾病、癌症和艾滋病在内的几种疾病的共同特征。因此，重要的是要了解细胞凋亡的过程，以便设计出干预和重置细胞生存和死亡之间的平衡的治疗手段。这项研究计划的目的是利用纳米颗粒结合的生物标记物来了解细胞凋亡。该方法依赖于用生物分子(细胞、多肽和酶)对固体表面进行修饰，然后使用电化学(循环伏安法、电化学阻抗谱)和光学(荧光光谱和表面等离子体共振)技术进行检测。该研究计划包括相互关联的子项目，涉及检测发生在质膜上的凋亡诱导的变化和细胞质中半胱氨酸天冬氨酸酶的激活。预期的结果应该会导致开发一种分析细胞凋亡的生物化学的方法。通过更好地了解凋亡途径，可能会开发出新的治疗药物来诱导癌细胞死亡。从这里提出的分析方法，将有可能指认和阐明大多数在细胞凋亡中的功能生物分子，并提供关于细胞反应和与纳米材料相互作用的信息。该研究计划将为阐明纳米材料及其与生物分子的相互作用提供独特的机会，如果我们最终要在全球范围内了解纳米材料在生物系统中的影响，这种分析方法是至关重要的。

Apoptosis has gained significant importance in human diseases and its clinical management. Failure to regulate apoptosis is a common feature in several diseases including neurodegenerative diseases, cancer, and AIDS. Hence, it is important to understand the apoptotic processes in order to devise therapeutic means to intervene and reset the balance between cell survival and death. The objective of this research program is to gain an understanding of apoptosis using nanoparticle-conjugated biomarkers. The methodology relies on the modification of solid surfaces with biomolecules (cells, peptides and enzymes) followed by the detection using electrochemical (cyclic voltammetry, electrochemical impedance spectroscopy) and optical (fluorescence spectroscopy and surface plasmon resonance) techniques. The research program includes interlinked sub-projects, which involve the detection of the apoptosis-induced changes that occur at the plasma membrane and the activation of caspases in the cytoplasm. The expected results should lead to the development of an analytical approach to the biological chemistry of apoptosis. By better understanding apoptosis pathways, novel therapeutic agents may be developed to induce death in cancerous cells. From the analytical approach proposed here, it will be possible to assign and elucidate the majority of functional biomolecules in apoptosis and provide information regarding cellular reactivity, and interactions with nanomaterials. The research plan will provide unique opportunities for the elucidation of nanomaterials and their interactions with biomolecules, and such analytical approaches are crucial, if we are to eventually understand the effect of nanomaterials in living systems on a global scale.