Interaction of Size-Tailored PEGylated Iron Oxide Nanoparticles with Lipid Membranes and Cells
Interaction of Size-Tailored PEGylated Iron Oxide Nanoparticles with Lipid Membranes and Cells
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DOI：
10.1021/acsbiomaterials.6b00311
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发表时间：
2017-03-01
影响因子：
5.8
通讯作者：
Reimhult, Erik
中科院分区：
文献类型：
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作者：
Gal, Noga;Lassenberger, Andrea;Reimhult, Erik
靶向纳米药物建立在这样的概念之上，即纳米颗粒可以定向到特定的组织，而对其他器官保持惰性。在核壳纳米粒子的合成和细胞相互作用方面已经进行了许多研究，其中功能无机核被生物相容的聚合物层覆盖，从而减少非特异性摄取和细胞毒性。然而，缺乏将核壳结构的结构参数和胶体性质直接与细胞膜的相互作用联系起来，并进一步将这些相互作用与细胞摄取联系起来的工作。我们合成了不同核尺寸(3-8 nm)的单分散(SD<；10%)、单晶和超顺磁性氧化铁纳米颗粒(SPION)，并将其密集地接枝到亚硝胺-聚乙二醇(NDA-PEG(5 KDa))刷子上。我们研究了聚乙二醇化的Spion与仿生膜以及癌细胞和肾细胞的相互作用。结果表明，致密均匀的聚乙二醇壳抑制了膜相互作用和细胞摄取，但纳米颗粒曲率会影响类似接枝纳米颗粒的膜相互作用。对阴离子类脂膜的弱吸附与真核细胞的摄取有关，并归因于没有直接膜渗透的双层相互作用。这种吸引力在生理条件下被强烈抑制，与传统的葡聚糖包被的Spion相比，导致前所未有的低细胞摄取率和完整的细胞存活率。弯曲程度较低(核心较大)的聚乙二醇化Spion由于有效致密的外壳，显示出较弱的膜吸附和较低的细胞摄取。这些结果有助于更好地理解核壳纳米颗粒在避免细胞非特异性摄取、降低毒性和增加循环时间方面的设计标准。
Targeted nanomedicine builds on the concept that nanoparticles can be directed to specific tissues while remaining inert to others organs. Many studies have been performed on the synthesis and cellular interactions of core-shell nanoparticles, in which a functional inorganic core is coated with a biocompatible polymer layer that should reduce nonspecific uptake and cytotoxicity. However, work is lacking that relates structural parameters of the core-shell structure and colloidal properties directly to interactions with cell membranes and further correlates these interactions to cell uptake. We have synthesized monodisperse (SD < 10%), single-crystalline, and superparamagnetic iron oxide nanoparticles (SPION) of different core size (3-8 nm) that are densely grafted with nitrodopamine-poly(ethylene glycol) (NDA-PEG(5 kDa)) brushes. We investigated the interactions of the PEGylated SPION with biomimetic membranes and cancer and kidney cells. It is shown that a dense homogeneous PEG shell suppresses membrane interactions and cell uptake but that nanoparticle curvature can influence membrane interactions for similarly grafted nanoparticles. Weak adsorption to anionic lipid membranes is shown to correlate with eukaryote cell uptake and is attributed to double-layer interactions without direct membrane penetration. This attraction is strongly suppressed during physiological conditions and leads to unprecedented low cell uptake and full cell viability when compared to those of traditional dextran-coated SPION. Less curved (larger core) PEGylated SPION show weaker membrane adsorption and lower cell uptake due to effectively denser shells. These results provide a better understanding of design criteria for core shell nanoparticles in terms of avoiding nonspecific uptake by cells, reducing toxicity, and increasing circulation time.