Quantification of the force of nanoparticle-cell membrane interactions and its influence on intracellular trafficking of nanoparticles.
Quantification of the force of nanoparticle-cell membrane interactions and its influence on intracellular trafficking of nanoparticles.
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DOI：
10.1016/j.biomaterials.2008.07.020
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发表时间：
2008-11
期刊：
影响因子：
14
通讯作者：
Labhasetwar, Vinod
中科院分区：
文献类型：
--
作者：
Vasir, Jaspreet K.;Labhasetwar, Vinod
了解纳米粒子(NPs)与细胞膜的相互作用及其在细胞中的转运对于充分探索利用NPs在细胞内有效地传递治疗药物是必要的。在这里，我们报道了一种利用原子力显微镜(AFM)测量NP细胞膜相互作用力的新方法。以聚L-赖氨酸功能化的聚乳酸-乙交酯共聚物纳米粒为模型体系，证明了这种作用力决定了纳米粒与细胞膜的黏附相互作用，进而决定了细胞对纳米粒的摄取程度，从而决定了微囊化治疗药物的摄取程度。用AFM成像监测细胞对NPs的摄取，并用共聚焦显微镜定量它们在细胞内的分布动态。结果表明，功能化的纳米粒子与细胞膜的粘附力是未修饰纳米粒子的5倍，原子力显微镜的时间推移图像显示其内化速度快于未修饰的纳米粒子。细胞内转运研究表明，功能化的NPs比未修饰的NPs更快、更有效地从晚期内吞体内逃逸，并导致包裹的模型蛋白在细胞内的输送增加了10倍。本文所描述的发现增强了我们对基于物理现象的NP-细胞膜相互作用的基本理解，这些物理现象可能在开发高效的纳米载体系统用于治疗药物的输送方面具有更广泛的应用。
Understanding the interaction of nanoparticles (NPs) with the cell membrane and their trafficking through cells is imperative to fully explore the use of NPs for efficient intracellular delivery of therapeutics. Here, we report a novel method of measuring the force of NP-cell membrane interactions using atomic force microscopy (AFM). Poly(dl-lactide co-glycolide, PLGA) NPs functionalized with poly-l-lysine were used as a model system, to demonstrate that this force determines the adhesive interaction of NPs with the cell membrane and in turn the extent of cellular uptake of NPs, and hence that of the encapsulated therapeutic. Cellular uptake of NPs was monitored using AFM imaging, and the dynamics of their intracellular distribution was quantified using confocal microscopy. Results demonstrated that the functionalized NPs have a five-fold greater force of adhesion with the cell membrane and the time-lapse AFM images show their rapid internalization than unmodified NPs. The intracellular trafficking study showed that the functionalized NPs escape more rapidly and efficiently from late endosomes than unmodified NPs and result in 10-fold higher intracellular delivery of the encapsulated model protein. The findings described herein enhance our basic understanding of the NP-cell membrane interaction on the basis of physical phenomena that could have wider applications in developing efficient nanocarrier systems for intracellular delivery of therapeutics.
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