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用于癌症治疗中药物递送的工程纳米颗粒。

Engineered nanoparticles for drug delivery in cancer therapy.

机构信息

The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332 (USA).

出版信息

Angew Chem Int Ed Engl. 2014 Nov 10;53(46):12320-64. doi: 10.1002/anie.201403036. Epub 2014 Oct 7.

Abstract

In medicine, nanotechnology has sparked a rapidly growing interest as it promises to solve a number of issues associated with conventional therapeutic agents, including their poor water solubility (at least, for most anticancer drugs), lack of targeting capability, nonspecific distribution, systemic toxicity, and low therapeutic index. Over the past several decades, remarkable progress has been made in the development and application of engineered nanoparticles to treat cancer more effectively. For example, therapeutic agents have been integrated with nanoparticles engineered with optimal sizes, shapes, and surface properties to increase their solubility, prolong their circulation half-life, improve their biodistribution, and reduce their immunogenicity. Nanoparticles and their payloads have also been favorably delivered into tumors by taking advantage of the pathophysiological conditions, such as the enhanced permeability and retention effect, and the spatial variations in the pH value. Additionally, targeting ligands (e.g., small organic molecules, peptides, antibodies, and nucleic acids) have been added to the surface of nanoparticles to specifically target cancerous cells through selective binding to the receptors overexpressed on their surface. Furthermore, it has been demonstrated that multiple types of therapeutic drugs and/or diagnostic agents (e.g., contrast agents) could be delivered through the same carrier to enable combination therapy with a potential to overcome multidrug resistance, and real-time readout on the treatment efficacy. It is anticipated that precisely engineered nanoparticles will emerge as the next-generation platform for cancer therapy and many other biomedical applications.

摘要

在医学领域,纳米技术引起了人们越来越浓厚的兴趣,因为它有望解决与传统治疗剂相关的许多问题,包括其较差的水溶性(至少对于大多数抗癌药物而言)、缺乏靶向能力、非特异性分布、全身毒性和低治疗指数。在过去的几十年中,在开发和应用工程纳米颗粒以更有效地治疗癌症方面取得了显著进展。例如,治疗剂已经与具有最佳尺寸、形状和表面特性的纳米颗粒集成在一起,以提高其溶解度、延长其循环半衰期、改善其生物分布并降低其免疫原性。还利用病理生理条件(例如,增强的通透性和保留效应以及 pH 值的空间变化),通过有利地将纳米颗粒及其有效载荷递送到肿瘤中。此外,靶向配体(例如,小分子、肽、抗体和核酸)已被添加到纳米颗粒的表面,通过与表面过表达的受体选择性结合,特异性地靶向癌细胞。此外,已经证明多种类型的治疗药物和/或诊断剂(例如,造影剂)可以通过同一载体递送来实现联合治疗,从而有可能克服多药耐药性,并实时读出治疗效果。预计经过精确设计的纳米颗粒将成为癌症治疗和许多其他生物医学应用的下一代平台。

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