Duskey Jason T, Rice Kevin G
Division of Medicinal and Natural Products Chemistry, College of Pharmacy, University of Iowa, Iowa City, Iowa, 52242, USA.
AAPS PharmSciTech. 2014 Oct;15(5):1345-54. doi: 10.1208/s12249-014-0143-6. Epub 2014 Jun 14.
Among the many scientific advances to come from the study of nanoscience, the development of ligand-targeted nanoparticles to eliminate solid tumors is predicted to have a major impact on human health. There are many reports describing novel designs and testing of targeted nanoparticles to treat cancer. While the principles of the technology are well demonstrated in controlled lab experiments, there are still many hurdles to overcome for the science to mature into truly efficacious targeted nanoparticles that join the arsenal of agents currently used to treat cancer in humans. One of these hurdles is overcoming unwanted biodistribution to the liver while maximizing delivery to the tumor. This almost certainly requires advances in both nanoparticle stealth technology and targeting. Currently, it continues to be a challenge to control the loading of ligands onto polyethylene glycol (PEG) to achieve maximal targeting. Nanoparticle cellular uptake and subcellular targeting of genes and siRNA also remain a challenge. This review examines the types of ligands that have been most often used to target nanoparticles to solid tumors. As the science matures over the coming decade, careful control over ligand presentation on nanoparticles of precise size, shape, and charge will likely play a major role in achieving success.
在纳米科学研究带来的众多科学进展中,开发用于消除实体瘤的配体靶向纳米颗粒预计将对人类健康产生重大影响。有许多报告描述了用于治疗癌症的靶向纳米颗粒的新颖设计和测试。虽然该技术的原理在可控的实验室实验中得到了充分证明,但要使这项科学发展成为真正有效的靶向纳米颗粒,并加入目前用于治疗人类癌症的药物库,仍有许多障碍需要克服。其中一个障碍是克服纳米颗粒在肝脏中的不必要生物分布,同时最大限度地将其递送至肿瘤。这几乎肯定需要纳米颗粒隐身技术和靶向技术的进步。目前,控制配体在聚乙二醇(PEG)上的负载以实现最大靶向性仍然是一个挑战。纳米颗粒对基因和小干扰RNA(siRNA)的细胞摄取和亚细胞靶向也仍然是一个挑战。这篇综述研究了最常用于将纳米颗粒靶向实体瘤的配体类型。随着未来十年该科学的成熟,对精确尺寸、形状和电荷的纳米颗粒上配体呈现的精确控制可能在取得成功方面发挥主要作用。