Phosphonate coating of commercial iron oxide nanoparticles for nanowarming cryopreserved samples.

Phosphonate coating of commercial iron oxide nanoparticles for nanowarming cryopreserved samples.
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DOI:
10.1039/d1tb02483c
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发表时间:
2022-05-18
影响因子:
7
通讯作者:
Bischof, John C.
Bischof, John C.
中科院分区:
工程技术2区
文献类型:
--
作者:
Pasek-Allen, Jacqueline L.;Wilharm, Randall K.;Gao, Zhe;Pierre, Valerie C.;Bischof, John C.

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新的保存技术可能允许器官银行类似于血液和生物材料银行的方法。使用冷冻保护剂(CPA),含有DMSO,丙二醇等有机成分的水溶液,以及添加的盐和糖,器官可以用于在-140 °C下玻璃化和储存器官。当需要时,这些器官可以以快速和均匀的方式复温,如果CPA在施加的射频场中补充氧化铁纳米颗粒(IONP)。升温的速度和均匀性均依赖于IONP浓度和CPA悬浮液。在这里,我们提出了一种小分子膦酸酯连接体(PLink)和生物相容性聚合物(即聚乙二醇PEG)的包衣方法,该方法可调节稳定性并增加CPA混悬液中IONP的最大允许浓度。PLink含有用于与氧化铁高度不可逆结合的膦酸酯“锚”和用于配体连接的羧酸“柄”。PLink-PEG去除并替换市售IONP(EMG 1200(疏水)和EMG 308(亲水))的初始涂层,Ferrotec,Inc.,从几分钟(未涂覆)到最多6天,增加胶体稳定性并减少在水和CPA两者中的聚集(用动态光散射验证)。使用360 kHz和20 kA m−1的外加场测量的EMG 1200的加热特性,即比吸收率(SAR),随着PLink-PEG 5000的增加,从20 W/g Fe增加到180 W/g Fe。PEG取代最初的疏水涂层减少聚集在水和CPA,与早期的研究一致的加热性能。此外,尽管在0.20 mol PEG/g Fe时尺寸最小化,但在EMG 1200上加热直到浓度高于0.43 mol PEG/g Fe时才最大化。亲水性EMG 308上的SAR保持在400 W/g Fe,而不管加入到芯中的PLink的量如何。在此,VS 55(普通CPA)中的IONP浓度显著高于我们先前的能力,达到了10 mg Fe/mL的sIONP,25 mg Fe/mL的308-PEG 5000和60 mg Fe/mL的1200-PEG 5000,接近于在水中的原液EMG 308,60 mg Fe/mL。此外,在这些浓度下,冷冻保存的人真皮成纤维细胞被成功地复温(在上述施加的场下),与水浴中的对流复温相比具有更高的活力,并且加热速率接近200 °C min-1,比我们目前的系统快2.5倍。使用PLink作为涂覆方法允许更高浓度的IONP成功地悬浮在CPA中而不影响加热能力。此外,模型配体PEG允许在配体化实验中随时间增加的稳定性。新的保存技术可能允许器官银行类似于血液和生物材料银行的方法。
New preservation technologies may allow for organ banking similar to blood and biomaterial banking approaches. Using cryoprotective agents (CPAs), aqueous solutions with organic components such as DMSO, propylene glycol, and added salts and sugars, organs can be used to vitrify and store organs at −140 °C. When needed, these organs can be rewarmed in a rapid and uniform manner if CPAs are supplemented with iron oxide nanoparticles (IONPs) in an applied radiofrequency field. Speed and uniformity of warming are both IONP concentration and CPA suspension dependent. Here we present a coating method of small molecule phosphonate linker (PLink) and biocompatible polymer (i.e. polyethylene glycol PEG) that tunes stability and increases the maximum allowable concentration of IONPs in CPA suspension. PLink contains a phosphonate 'anchor' for high irreversible binding to iron oxide and a carboxylic acid 'handle' for ligand attachment. PLink-PEG removes and replaces the initial coating layer of commercially available IONPs (EMG1200 (hydrophobic) and EMG308 (hydrophilic) Ferrotec, Inc., increasing colloidal stability and decreasing aggregation in both water and CPAs, (verified with dynamic light scattering) from minutes (uncoated) to up to 6 days. Heating properties of EMG1200, specific absorption rate (SAR), measured using an applied field of 360 kHz and 20 kA m−1, increased from 20 to 180 W per g Fe with increasing PLink-PEG5000. PEG replacing the initially hydrophobic coating decreased aggregation in water and CPA, consistent with earlier studies on heating performance. Furthermore, although the size is minimized at 0.20 mol PEG per g Fe, heating is not maximized until concentrations above 0.43 mol PEG per g Fe on EMG1200. SAR on hydrophilic EMG308 was preserved at 400 W per g Fe regardless of the amount of PLink added to the core. Herein concentrations of IONP in VS55 (common CPA) significantly above our previous capabilities, sIONP at 10 mg Fe per mL, was reached, 25 mg Fe per mL of 308-PEG5000 and 60 mg Fe per mL of 1200-PEG5000, approaching stock EMG308 in water, 60 mg Fe per mL. Furthermore, at these concentrations cryopreserved Human dermal fibroblast cells were successfully nanowarmed (at applied fields described above), with higher viability as compared to convective rewarming in a water bath and heating rate close to 200 °C min−1, 2.5 times faster than our current system. Using PLink as the coating method allowed for higher concentrations of IONPs to be successfully suspended in CPA without affecting the heating ability. Additionally, the model ligand, PEG, allowed for increased stability over time in nanowarming experiments. New preservation technologies may allow for organ banking similar to blood and biomaterial banking approaches.
DOI: 10.1142/s2339547814500204
发表时间: 2014-09-01
期刊: TECHNOLOGY
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