Nanotechnology has been applied extensively in drug delivery to improve the therapeutic outcomes of various diseases. Tremendous efforts have been focused on the development of novel nanoparticles and delineation of the physicochemical properties of nanoparticles in relation to their biological fate and functions. However, in the design and evaluation of these nanotechnology-based drug delivery systems, the pharmacology of delivered drugs and the (patho-)physiology of the host have received less attention. In this review, we discuss important pharmacological mechanisms, physiological characteristics, and pathological factors that have been integrated into the design of nanotechnology-enabled drug delivery systems and therapies. Firsthand examples are presented to illustrate the principles and advantages of such integrative design strategies for cancer treatment by exploiting 1) intracellular synergistic interactions of drug-drug and drug-nanomaterial combinations to overcome multidrug-resistant cancer, 2) the blood flow direction of the circulatory system to maximize drug delivery to the tumor neovasculature and cells overexpressing integrin receptors for lung metastases, 3) endogenous lipoproteins to decorate nanocarriers and transport them across the blood-brain barrier for brain metastases, and 4) distinct pathological factors in the tumor microenvironment to develop pH- and oxidative stress-responsive hybrid manganese dioxide nanoparticles for enhanced radiotherapy. Regarding the application in diabetes management, a nanotechnology-enabled closed-loop insulin delivery system was devised to provide dynamic insulin release at a physiologically relevant time scale and glucose levels. These examples, together with other research results, suggest that utilization of the interplay of pharmacology, (patho-)physiology and nanotechnology is a facile approach to develop innovative drug delivery systems and therapies with high efficiency and translational potential.

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将纳米技术与药理学和生理学结合在一起以进行创新的药物递送和治疗的重要性-带有第一手实例的插图。

纳米技术已广泛应用于药物输送中，以改善各种疾病的治疗效果。大量的努力集中在新型纳米颗粒的开发以及与它们的生物学命运和功能有关的纳米颗粒的理化特性的描绘上。然而，在这些基于纳米技术的药物递送系统的设计和评估中，递送药物的药理学和宿主的（病理）生理学受到的关注较少。在这篇综述中，我们讨论了重要的药理机制，生理特征和病理因素，这些因素已被整合到纳米技术支持的药物递送系统和疗法的设计中。第一手实例说明了这种综合设计策略在癌症治疗中的原理和优势，方法是：1）药物与药物-纳米材料组合的细胞内协同相互作用克服多药耐药性癌症； 2）循环系统的血流方向该系统可最大程度地将药物递送至肿瘤新脉管系统和过度表达整合素受体的肺转移细胞； 3）内源性脂蛋白修饰纳米载体，并通过血脑屏障转运至脑转移，以及4）肿瘤微环境中独特的病理因素发展pH和氧化应激响应的混合二氧化锰纳米粒子，用于增强放射治疗。关于在糖尿病管理中的应用，设计了纳米技术的闭环胰岛素输送系统，以在生理相关的时间尺度和葡萄糖水平下提供动态胰岛素释放。这些例子以及其他研究结果表明，利用药理学，（病理）生理学和纳米技术的相互作用是开发高效和具有转化潜力的创新药物递送系统和疗法的简便方法。