Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, Massachusetts 02115, USA.
Acc Chem Res. 2011 Oct 18;44(10):1009-17. doi: 10.1021/ar2000106. Epub 2011 Jul 15.
By definition, multifunctional nanosystems include several features within a single construct so that these devices can target tumors or other disease tissue, facilitate in vivo imaging, and deliver a therapeutic agent. Investigations of these nanosystems are rapidly progressing and provide new opportunities in the management of cancer. Tumor-targeted nanosystems are currently designed based primarily on the intrinsic physico-chemical properties of off-the-shelf polymers. Following fabrication, the surfaces of these nanoscale structures are functionalized for passive or active targeted delivery to the tumors. In this Account, we describe a novel approach for the construction of multifunctional polymeric nanosystems based on combinatorial design principles. Combinatorial approaches offer several advantages over conventional methods because they allow for the integration of multiple components with varied properties into a nanosystem via self-assembly or chemical conjugation. High-throughput synthesis and screening is required in polymer design because polymer composition directly affects properties including drug loading, retention in circulation, and targeting of the nanosystems. The first approach relies on the self-assembly of macromolecular building blocks with specific functionalities in aqueous media to yield a large variety of nanoparticle systems. These self-assembled nanosystems with diverse functionalities can then be rapidly screened in a high-throughput fashion for selection of ideal formulations, or hits, which are further evaluated for safety and efficacy. In another approach, a library of a large number of polymeric materials is synthesized using different monomers. Each of the formed polymers is screened for the selection of the best candidates for nanoparticle fabrication. The combinatorial design principles allow for the selection of those nanosystems with the most favorable properties based on the type of payload, route of administration, and the desired target for imaging and delivery.
根据定义，多功能纳米系统在单个构建体中包含多个特征，以便这些设备可以靶向肿瘤或其他疾病组织，促进体内成像，并输送治疗剂。这些纳米系统的研究正在迅速推进，并为癌症的治疗提供了新的机会。肿瘤靶向纳米系统目前主要基于现成聚合物的固有物理化学性质进行设计。在制造之后，这些纳米级结构的表面被官能化，以进行被动或主动靶向递送至肿瘤。在本述评中，我们描述了一种基于组合设计原理构建多功能聚合物纳米系统的新方法。组合方法相对于传统方法具有几个优势，因为它们允许通过自组装或化学偶联将具有不同性质的多个组件集成到纳米系统中。在聚合物设计中需要高通量合成和筛选，因为聚合物组成直接影响包括药物负载、在循环中的保留和纳米系统靶向在内的性质。第一种方法依赖于具有特定功能的大分子构建块在水介质中的自组装，以产生各种纳米颗粒系统。这些具有多种功能的自组装纳米系统可以快速进行高通量筛选，以选择理想的配方，即命中，然后进一步评估安全性和功效。在另一种方法中，使用不同的单体合成了大量的聚合物材料库。形成的每一种聚合物都经过筛选，以选择用于纳米颗粒制造的最佳候选聚合物。组合设计原则允许根据有效载荷的类型、给药途径以及成像和递送至的预期目标，选择具有最有利性质的纳米系统。
