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首页> 外文期刊>Life sciences >Multidimensional atomic force microscopy for drug discovery: a versatile tool for defining targets, designing therapeutics and monitoring their efficacy.
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Multidimensional atomic force microscopy for drug discovery: a versatile tool for defining targets, designing therapeutics and monitoring their efficacy.

机译：用于药物发现的多维原子力显微镜：定义目标，设计治疗方法和监测其功效的多功能工具。

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Current therapeutic design involves combinatorial chemistry and system biology-based molecular synthesis and bulk pharmacological assays. Therapeutics delivery is usually non-specific to disease targets and requires excessive dosage. Efficient therapeutic discovery and delivery would require molecular level understanding of the therapeutics-effectors (e.g., channels and receptors) interactions and their cell and tissue responses. This review summarizes the application of multidimensional scanning probe techniques, especially atomic force microscopy (AFM), for drug discovery. Important features of AFM include its capability of atomic scale structural and physical properties study of live biological systems, its open architecture that allows its integration with other techniques, tools and operating environments, and its application for creating and characterizing nanocarriers and implantable vehicles for controlled delivery. Specific areas covered include: 1) the operating principle and examples of AFM integrated with electrical recording, fluorescence imaging and microfluidics, (2) examples of AFM nanoscale imaging that has provided new paradigms in pathogenesis, including protein misfolding diseases (e.g., Alzheimer's disease, cancer, diabetes) and diseases arising from environmental and life choices and thus identifies potential therapeutic targets, (3) high-throughput parallel sensors, comprising integrated cantilevered microarrays, TIRF, microfluidics and nanoelectronics, for potential rapid diagnosis of pathogens, allergens and biomarkers as well as for therapeutics design, (4) the definition target macromolecules and structures, using intermolecular interaction assays, (5) the definition of abnormal vs normal tissues and the assessment of therapeutic efficacy by monitoring biomechanics, and (6) the development and characterization of nanocarrier-based drug delivery (e.g., nanoliposomes and nanoparticles) systems that allow high efficiency in vivo or the topical administration of a small dosage of therapeutics.
机译：当前的治疗设计涉及基于组合化学和系统生物学的分子合成和大量药理测定。治疗药物的递送通常对疾病目标没有特异性，需要过量的剂量。有效的治疗发现和递送将需要分子水平了解治疗剂-效应子（例如，通道和受体）的相互作用及其对细胞和组织的反应。这篇综述总结了多维扫描探针技术，尤其是原子力显微镜（AFM）在药物发现中的应用。原子力显微镜的重要特征包括其对活生物系统进行原子尺度结构和物理性质研究的能力，允许与其他技术，工具和操作环境集成的开放式体系结构以及其在创建和表征纳米载体和可植入载体以控制递送方面的应用。涵盖的具体领域包括：1）AFM与电记录，荧光成像和微流控技术相集成的操作原理和示例;（2）AFM纳米级成像的示例提供了发病机理的新范例，包括蛋白质错误折叠疾病（例如阿尔茨海默氏病， （癌症，糖尿病）和因环境和生活选择而引起的疾病，从而确定潜在的治疗目标;（3）高通量并行传感器，包括集成的悬臂微阵列，TIRF，微流控技术和纳米电子技术，可用于病原体，过敏原和生物标记物的快速诊断以及用于治疗设计，（4）使用分子间相互作用分析确定目标大分子和结构，（5）定义正常组织与正常组织的区别，以及通过监测生物力学评估治疗效果，以及（6）开发和表征基于纳米载体的药物递送（例如，纳米脂质体和纳米颗粒） cles）系统，可在体内或局部使用小剂量的治疗剂进行高效治疗。

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