Multifunctional Cytotoxic Stealth Nanoparticles. A Model Approach with Potential for Cancer Therapy
Multifunctional Cytotoxic Stealth Nanoparticles. A Model Approach with Potential for Cancer Therapy
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DOI：
10.1021/nl802990w
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发表时间：
2009-02-01
期刊：
影响因子：
10.8
通讯作者：
Decher, Gero
中科院分区：
文献类型：
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作者：
Schneider, Gregory F.;Subr, Vladimir;Decher, Gero
在这里，我们报告了一个高度通用的纳米粒子为基础的核/壳药物输送系统组成的细胞毒性隐形载体颗粒。它们的多功能外壳是解决不同诊断/治疗要求的必备工具，使用单一组装工艺构建，其中以模块化方式整合了各种不同的功能。更具体地说，我们讨论了一个强大的静电和共价逐层（LBL）组装策略，作为工程方法的纳米粒子与多层壳，结合联合收割机所有以下属性：（i）纳米颗粒载体的小尺寸分布，（ii）在生理介质中的高稳定性，（iii）前药以共价形式附着，因此载体系统的低毒性，（iv）仅在胞吞作用和酶裂解后药物的触发释放和活化，和（v）“隐蔽性”，从而防止被巨噬细胞摄取。我们采用小纳米颗粒作为载体的事实被预测会增强活性药物在肿瘤组织中的积累（即，增强的渗透性和肿瘤组织的保留，EPR）。为了建立该系统作为概念验证，我们使用在约25-100 nm的感兴趣尺寸范围内的最小纳米颗粒用于EPR靶向，因为这些是最难官能化的，并且因为它们具有最高的表面积。基于金纳米颗粒核，我们的系统可以精确控制颗粒尺寸和尺寸分布，并通过肉眼轻松监控分散稳定性。
Here we report on a highly versatile nanoparticle-based core/shell drug delivery system consisting of cytotoxic stealth carrier particles. Their multifunctional shells, mandatory for addressing different diagnostic/treatment requirements, are constructed using a single assembly process in which various different functionalities are incorporated in a modular fashion. More specifically, we discuss a robust electrostatic and covalent layer-by-layer (LBL) assembly strategy as engineering approach toward nanoparticles with multilayer shells that combine all of the following properties: (i) a small size distribution of the nanoparticle carrier, (ii) a high stability in physiological media, (iii) attachment of a pro-drug in covalent form and thus a low toxicity of the carrier system, (iv) the triggered release and activation of the drug only after endocytosis and enzymatic cleavage, and (v) "stealthiness" and thus protection against uptake by macrophages. The fact that we employ small nanoparticles as carriers is predicted to enhance the accumulation of active drug in the tumor tissue (i.e., enhanced permeability and retention of tumor tissues, EPR). To establish this system as a proof of concept, we use the smallest nanoparticles within the interesting size range of about 25-100 nm for EPR targeting since these are the most difficult to functionalize and because they possess the highest surface area. On the basis of gold nanoparticle cores, our system allows for precise control of particle size and size distribution and also for easy monitoring of the dispersion stability by the naked eye.