Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
Acc Chem Res. 2011 Oct 18;44(10):999-1008. doi: 10.1021/ar200094a. Epub 2011 Jul 14.
The increasing importance of nanotechnology in the biomedical field and the recent progress of nanomedicines into clinical testing have spurred the development of even more sophisticated nanoscale drug carriers. Current nanocarriers can successfully target cells, release their cargo in response to stimuli, and selectively deliver drugs. More sophisticated nanoscale carriers should evolve into fully integrated vehicles with more complex capabilities. First, they should be able to sense targets inside the body and adapt their functions based on these targets. Such devices will also have processing capabilities, modulating their properties and functions in response to internal or external stimuli. Finally, they will direct their function to the aimed site through both subcellular targeting and delivery of loaded drugs. These nanoscale, multifunctional drug carriers are defined here as nanodevices. Through the integration of various imaging elements into their design, the nanodevices can be made visible, which is an essential feature for the validation. The visualization of nanodevices also facilitates their use in the clinic: clinicians can observe the effectiveness of the devices and gain insights into both the disease progression and the therapeutic response. Nanodevices with this dual diagnostic and therapeutic function are called theranostic nanodevices. In this Account, we describe various challenges to be overcome in the development of smart nanodevices based on supramolecular assemblies of engineered block copolymers. In particular, we focus on polymeric micelles. Polymeric micelles have recently received considerable attention as a promising vehicle for drug delivery, and researchers are currently investigating several micellar formulations in preclinical and clinical studies. By engineering the constituent block copolymers to produce polymeric micelles that integrate multiple smart functionalities, we and other researchers are developing nanodevices with favorable clinical properties.
纳米技术在生物医学领域的重要性日益增加，纳米药物最近也进入临床测试阶段，这促使人们开发出更复杂的纳米级药物载体。目前的纳米载体可以成功靶向细胞，根据刺激释放其货物，并选择性地输送药物。更复杂的纳米级载体应该演变成具有更复杂功能的完全集成的载体。首先，它们应该能够感知体内的靶标，并根据这些靶标调整它们的功能。这种装置还将具有处理能力，能够根据内部或外部刺激来调节其性质和功能。最后，它们将通过亚细胞靶向和载药的输送，将其功能指向目标部位。这些纳米级多功能药物载体在这里被定义为纳米器件。通过将各种成像元件集成到它们的设计中，纳米器件可以变得可见，这是验证的一个基本特征。纳米器件的可视化也便于它们在临床上的使用：临床医生可以观察到设备的有效性，并深入了解疾病的进展和治疗反应。具有这种双重诊断和治疗功能的纳米器件被称为治疗诊断纳米器件。在本账户中，我们描述了基于工程嵌段共聚物的超分子组装开发智能纳米器件所面临的各种挑战。特别是，我们专注于聚合物胶束。聚合物胶束最近作为一种很有前途的药物输送载体受到了相当多的关注，研究人员目前正在临床前和临床研究中研究几种胶束配方。通过对组成嵌段共聚物进行工程设计，生成集成多种智能功能的聚合物胶束，我们和其他研究人员正在开发具有良好临床特性的纳米器件。
