Controlled aggregation and cell uptake of thermoresponsive polyoxazoline-grafted superparamagnetic iron oxide nanoparticles
Controlled aggregation and cell uptake of thermoresponsive polyoxazoline-grafted superparamagnetic iron oxide nanoparticles
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DOI：
10.1039/c6nr08654c
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发表时间：
2017-02-28
期刊：
影响因子：
6.7
通讯作者：
Reimhult, Erik
中科院分区：
文献类型：
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作者：
Kurzhals, Steffen;Gal, Noga;Reimhult, Erik
亲水性聚合物包覆的氧化铁纳米颗粒是生物技术领域中大量应用的潜在材料。典型的此类聚合物，e. G.葡聚糖或聚（乙二醇）缺乏调整对环境触发的生物反应的能力，而普通的响应性聚合物如聚（N-异丙基丙烯酰胺）或聚（丙烯酸）不适合于生物医学应用。我们目前的合成和表征的超顺磁性氧化铁纳米粒子的温敏聚恶唑啉刷接枝在前所未有的密度使用硝基多巴胺锚化学。在水和生物介质中观察到可逆的聚集/解聚，证实了对胶体稳定性的控制。溶解度的热切换只能通过样品的全局加热来实现，而局部磁热加热没有通过刷子产生足够强的温度梯度。改变聚合物组成允许调节较低临界溶解温度（LCST）以及在加热时获得的平均纳米颗粒簇尺寸。聚恶唑啉的LCST和热胶体稳定性被证明是由离子浓度，聚合物接枝密度和血清蛋白的存在下，也有很大的影响;这表明，在水中的自由聚合物的转变温度可以是非常误导的聚合物涂层的纳米材料的生物医学应用的设计。最后，温敏SPION被证明是无细胞毒性的，并且具有低的细胞摄取比例与聚合物刷的水合作用，这是由聚合物组合物调整。因此，我们证明，pozylated纳米粒子提供的PEG和PNIPAM接枝的纳米粒子的优点，但提供了一个可调的和更容易官能化的平台，用于进一步的发展。
Hydrophilic polymer-coated iron oxide nanoparticles are potential materials for a plethora of applications in the biotechnological field. Typical such polymers, e. g. dextran or poly(ethylene glycol), lack the ability to tailor the biological response to an environmental trigger, while common responsive polymers such as poly(N-isopropylacrylamide) or poly(acrylic acid) are not suitable for biomedical applications. We present the synthesis and characterization of superparamagnetic iron oxide nanoparticles with thermoresponsive polyoxazoline brushes grafted at unprecedented density using nitrodopamine anchor chemistry. Reversible aggregation/deaggregation is observed in water and biological medium, confirming control over the colloidal stability. Thermal switching of the solubility could only be achieved by global heating of the sample, while local magnetothermal heating did not produce a sufficiently strong temperature gradient through the brush. Varying the polymer composition allows for tuning of the lower critical solution temperature (LCST) as well as the average nanoparticle cluster size obtained upon heating. The LCST of polyoxazolines and the thermal colloidal stability are shown to be greatly affected by ion concentration, by polymer grafting density and also by the presence of serum protein; this shows that transition temperatures of free polymers in water can be very misleading for the design of polymer-coated nanomaterials for biomedical applications. Finally, the thermoresponsive SPION are shown to be non-cytotoxic and with a low cell uptake scaling with the hydration of the polymer brush, which is tuned by the polymer composition. Thus, we demonstrate that pozylated nanoparticles provide the advantages of PEG- and PNIPAM-grafted nanoparticles, but provide a tunable and more easily functionalizable platform for further development.