树状高分子纳米医学的新兴概念:从设计原理到临床应用。
Emerging concepts in dendrimer-based nanomedicine: from design principles to clinical applications.
机构信息
Department of Ophthalmology, Center for Nanomedicine, Baltimore, MD, USA.
出版信息
J Intern Med. 2014 Dec;276(6):579-617. doi: 10.1111/joim.12280. Epub 2014 Jul 31.
Dendrimers are discrete nanostructures/nanoparticles with 'onion skin-like' branched layers. Beginning with a core, these nanostructures grow in concentric layers to produce stepwise increases in size that are similar to the dimensions of many in vivo globular proteins. These branched tree-like concentric layers are referred to as 'generations'. The outer generation of each dendrimer presents a precise number of functional groups that may act as a monodispersed platform for engineering favourable nanoparticle-drug and nanoparticle-tissue interactions. These features have attracted significant attention in medicine as nanocarriers for traditional small drugs, proteins, DNA/RNA and in some instances as intrinsically active nanoscale drugs. Dendrimer-based drugs, as well as diagnostic and imaging agents, are emerging as promising candidates for many nanomedicine applications. First, we will provide a brief survey of recent nanomedicines that are either approved or in the clinical approval process. This will be followed by an introduction to a new 'nanoperiodic' concept which proposes nanoparticle structure control and the engineering of 'critical nanoscale design parameters' (CNDPs) as a strategy for optimizing pharmocokinetics, pharmocodynamics and site-specific targeting of disease. This paradigm has led to the emergence of CNDP-directed nanoperiodic property patterns relating nanoparticle behaviour to critical in vivo clinical translation issues such as cellular uptake, transport, elimination, biodistribution, accumulation and nanotoxicology. With a focus on dendrimers, these CNDP-directed nanoperiodic patterns are used as a strategy for designing and optimizing nanoparticles for a variety of drug delivery and imaging applications, including a recent dendrimer-based theranostic nanodevice for imaging and treating cancer. Several emerging preclinical dendrimer-based nanotherapy concepts related to inflammation, neuro-inflammatory disorders, oncology and infectious and ocular diseases are reviewed. Finally we will consider challenges and opportunities anticipated for future clinical translation, nanotoxicology and the commercialization of nanomedicine.
树突状聚合物是具有“洋葱皮状”分支层的离散纳米结构/纳米粒子。从核心开始,这些纳米结构在同心层中生长,导致尺寸逐步增加,类似于许多体内球形蛋白质的尺寸。这些分支树状同心层被称为“代”。每个树突状聚合物的最外层呈现出精确数量的功能基团,这些功能基团可以作为工程有利的纳米药物和纳米组织相互作用的单分散平台。这些特性作为传统小分子药物、蛋白质、DNA/RNA 的纳米载体,以及在某些情况下作为固有活性的纳米级药物,在医学中引起了广泛关注。基于树突状聚合物的药物以及诊断和成像剂作为许多纳米医学应用的有前途的候选物正在出现。首先,我们将简要介绍已经批准或正在临床批准过程中的一些最新的纳米药物。其次,我们将介绍一种新的“纳米周期性”概念,该概念提出控制纳米颗粒结构和工程“关键纳米设计参数”(CNDPs)作为优化药代动力学、药效学和疾病部位靶向的策略。这种范例导致了与关键体内临床转化问题(如细胞摄取、转运、消除、生物分布、积累和纳米毒理学)相关的纳米颗粒行为与关键纳米周期性性质模式相关的 CNDP 导向的纳米周期性性质模式的出现。重点关注树突状聚合物,这些 CNDP 导向的纳米周期性模式被用作设计和优化各种药物输送和成像应用的纳米颗粒的策略,包括最近用于成像和治疗癌症的基于树突状聚合物的治疗学纳米设备。综述了几种新兴的基于树突状聚合物的纳米治疗学概念,涉及炎症、神经炎症性疾病、肿瘤学以及传染病和眼部疾病。最后,我们将考虑未来临床转化、纳米毒理学和纳米医学商业化的挑战和机遇。