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主动和被动靶向策略概述,以提高纳米载体向肿瘤部位的传递效率。

An overview of active and passive targeting strategies to improve the nanocarriers efficiency to tumour sites.

机构信息

CNRS, CAMB, UMR 7199, Université de Strasbourg, Strasbourg, France.

Department of Bioengineering, Clemson University, Clemson, SC, USA.

出版信息

J Pharm Pharmacol. 2019 Aug;71(8):1185-1198. doi: 10.1111/jphp.13098. Epub 2019 May 3.

Abstract

OBJECTIVES

This review highlights both the physicochemical characteristics of the nanocarriers (NCs) and the physiological features of tumour microenvironment (TME) to outline what strategies undertaken to deliver the molecules of interest specifically to certain lesions. This review discusses these properties describing the convenient choice between passive and active targeting mechanisms with details, illustrated with examples of targeting agents up to preclinical research or clinical advances.

KEY FINDINGS

Targeted delivery approaches for anticancers have shown a steep rise over the past few decades. Though many successful preclinical trials, only few passive targeted nanocarriers are approved for clinical use and none of the active targeted nanoparticles. Herein, we review the principles and for both processes and the correlation with the tumour microenvironment. We also focus on the limitation and advantages of each systems regarding laboratory and industrial scale.

SUMMARY

The current literature discusses how the NCs and the enhanced permeation and retention effect impact the passive targeting. Whereas the active targeting relies on the ligand-receptor binding, which improves selective accumulation to targeted sites and thus discriminates between the diseased and healthy tissues. The latter could be achieved by targeting the endothelial cells, tumour cells, the acidic environment of cancers and nucleus.

摘要

目的

本综述重点介绍了纳米载体(NCs)的物理化学特性和肿瘤微环境(TME)的生理特征,概述了为将感兴趣的分子特异性递送至特定病变部位而采取的哪些策略。本综述讨论了这些特性,详细描述了被动和主动靶向机制之间的便捷选择,并通过靶向试剂的实例说明了从临床前研究到临床进展的情况。

主要发现

在过去几十年中,针对癌症的靶向递送方法有了显著的发展。尽管有许多成功的临床前试验,但只有少数被动靶向纳米载体被批准用于临床应用,也没有主动靶向纳米颗粒。本文综述了这两种方法的原理,以及它们与肿瘤微环境的相关性。我们还重点介绍了每个系统在实验室和工业规模上的局限性和优势。

总结

目前的文献讨论了 NCs 和增强的渗透和保留效应如何影响被动靶向。而主动靶向则依赖于配体-受体结合,这可以改善对靶向部位的选择性积累,从而区分疾病和健康组织。后者可以通过靶向内皮细胞、肿瘤细胞、癌症的酸性环境和细胞核来实现。

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