Effect of polyethyleneglycol (PEG) chain length on the bio-nano-interactions between PEGylated lipid nanoparticles and biological fluids: from nanostructure to uptake in cancer cells
Effect of polyethyleneglycol (PEG) chain length on the bio-nano-interactions between PEGylated lipid nanoparticles and biological fluids: from nanostructure to uptake in cancer cells
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DOI：
10.1039/c3nr05559k
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发表时间：
2014-01-01
期刊：
影响因子：
6.7
通讯作者：
Lagana, Aldo
中科院分区：
文献类型：
--
作者：
Pozzi, Daniela;Colapicchioni, Valentina;Lagana, Aldo
当纳米颗粒（NP）进入生理环境时，介质组分竞争结合到NP表面，导致形成称为“蛋白质冠”的丰富蛋白质壳。不幸的是，调理素也被吸附。这些蛋白质立即被吞噬细胞系统识别，并从血流中快速清除NP。纳米颗粒的聚乙二醇（PEG）涂层（PEG化）是最有效的抗调理素化策略。接枝到NP表面上的PEG的线性链能够产生空间位阻，导致蛋白质吸附的显著抑制和巨噬细胞的较少识别。然而，过度的PEG化可导致细胞摄取的强烈抑制和与蛋白质靶标的较低效率的结合，从而降低递送系统的潜力。为了在这方面达成妥协，我们采用了多组分（MC）脂质系统，具有细胞摄取和内体逃逸的不寻常特性以及PEG链长度的增加。纳米液相色谱-串联质谱（nanoLC-MS/ MS）分析使我们能够准确地确定冠组成，表明载脂蛋白是冠中最丰富的一类，增加PEG长度降低了蛋白质吸附和脂质体表面对载脂蛋白的亲和力。由于载脂蛋白的丰度，我们利用“蛋白质冠效应”将阳离子脂质体-人血浆复合物递送至表达高水平的清道夫受体B类1型的人前列腺癌PC 3细胞，以评估所用系统的细胞摄取效率。在PC 3细胞中结合激光扫描共聚焦显微镜和流式细胞术分析，我们证明MC-PEG 2k是抗调理素策略和主动靶向之间的最佳折衷，并且可能是体内治疗前列腺癌的有希望的候选者。
When nanoparticles (NPs) enter a physiological environment, medium components compete for binding to the NP surface leading to formation of a rich protein shell known as the "protein corona". Unfortunately, opsonins are also adsorbed. These proteins are immediately recognized by the phagocyte system with rapid clearance of the NPs from the bloodstream. Polyethyleneglycol (PEG) coating of NPs (PEGylation) is the most efficient anti-opsonization strategy. Linear chains of PEG, grafted onto the NP surface, are able to create steric hindrance, resulting in a significant inhibition of protein adsorption and less recognition by macrophages. However, excessive PEGylation can lead to a strong inhibition of cellular uptake and less efficient binding with protein targets, reducing the potential of the delivery system. To reach a compromise in this regard we employed a multi-component (MC) lipid system with uncommon properties of cell uptake and endosomal escape and increasing length of PEG chains. Nano liquid chromatography coupled with tandem mass spectrometry (nanoLC-MS/ MS) analysis allowed us to accurately determine the corona composition showing that apolipoproteins are the most abundant class in the corona and that increasing the PEG length reduced the protein adsorption and the liposomal surface affinity for apolipoproteins. Due to the abundance of apolipoproteins, we exploited the "protein corona effect" to deliver cationic liposome-human plasma complexes to human prostate cancer PC3 cells that express a high level of scavenger receptor class B type 1 in order to evaluate the cellular uptake efficiency of the systems used. Combining laser scanning confocal microscopy with flow cytometry analysis in PC3 cells we demonstrated that MC-PEG2k is the best compromise between an anti-opsonization strategy and active targeting and could be a promising candidate to treat prostate cancer in vivo.