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纳米颗粒与血浆蛋白的相互作用:对药物递送系统的清除和毒性的影响。

Interactions of nanoparticles with plasma proteins: implication on clearance and toxicity of drug delivery systems.

机构信息

Sanford-Burnham Medical Research Institute, Cancer Research Center, La Jolla, CA 92037, USA.

出版信息

Expert Opin Drug Deliv. 2011 Mar;8(3):343-57. doi: 10.1517/17425247.2011.554818. Epub 2011 Feb 4.

DOI:10.1517/17425247.2011.554818
PMID:21291354
Abstract

INTRODUCTION

Intravenously injected nanoparticles, like any other foreign pathogen that enters the body, encounter multiple lines of defense intended to neutralize and eliminate the invading substance. Adsorption of plasma proteins on the nanoparticle surface is the first barrier of defense, which could lead to physical changes in the formulation, such as aggregation and charge neutralization, biochemical activation of defense cascades, and trigger elimination by multiple types of phagocytic cell.

AREAS COVERED

In this review, recent knowledge on the mechanisms that govern the interactions of nanoparticles (micelles, liposomes, polymeric and inorganic nanoparticles) with plasma proteins is discussed. In particular, the role of the nanoparticle surface properties and protective polymer coating in these interactions is described. The mechanisms of protein adsorption on different nanoparticles are analyzed and the implications on the clearance, toxicity and efficacy of drug delivery are discussed. The review provides readers with the biological insight into the plasma/blood interactions of nanoparticles.

EXPERT OPINION

The immune recognition of nanoparticles can seriously affect the drug delivery efficacy and toxicity. There is at present not enough knowledge on the mechanisms that dictate the nanoparticle immune recognition and stability in the biological milieu. Understanding the mechanisms of recognition will become an important part of nanoparticle design.

摘要

简介

静脉注射的纳米粒子,像任何其他进入体内的外来病原体一样,会遇到旨在中和和消除入侵物质的多重防御线。血浆蛋白在纳米粒子表面的吸附是第一道防线,这可能导致制剂发生物理变化,如聚集和电荷中和、防御级联的生化激活,并触发多种吞噬细胞的消除。

涵盖领域

在这篇综述中,讨论了最近关于控制纳米粒子(胶束、脂质体、聚合物和无机纳米粒子)与血浆蛋白相互作用的机制的知识。特别描述了纳米粒子表面性质和保护聚合物涂层在这些相互作用中的作用。分析了不同纳米粒子上蛋白质吸附的机制,并讨论了其对药物递送的清除、毒性和功效的影响。该综述为读者提供了关于纳米粒子在血浆/血液中相互作用的生物学见解。

专家意见

纳米粒子的免疫识别可能严重影响药物输送的功效和毒性。目前对于决定纳米粒子在生物环境中的免疫识别和稳定性的机制还没有足够的了解。了解识别机制将成为纳米粒子设计的重要组成部分。

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