High-relaxivity superparamagnetic iron oxide nanoworms with decreased immune recognition and long-circulating properties.
High-relaxivity superparamagnetic iron oxide nanoworms with decreased immune recognition and long-circulating properties.
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DOI：
10.1021/nn505126b
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发表时间：
2014-12-23
期刊：
影响因子：
17.1
通讯作者：
Simberg D
中科院分区：
文献类型：
--
作者：
Wang G;Inturi S;Serkova NJ;Merkulov S;McCrae K;Russek SE;Banda NK;Simberg D
纳米技术的核心问题之一涉及掩盖纳米材料的外来性，以实现体内寿命和长期免疫逃避。右旋糖酐包被的超顺磁性氧化铁纳米颗粒是非常有效的磁共振成像（MRI）造影剂，防止免疫识别的策略对其临床转化至关重要。本文制备了直径为250 nm、高摩尔横向放宽率R2 （~400 mM−1 s−1）的20 kDa右旋糖酐包被SPIO纳米蠕虫（NWs），研究了与1-氯-2,3-环氧丙烷（环氧氯丙烷）交联水凝胶化对体外和体内免疫逃逸的影响。在不同的NaOH浓度（0.5 ~ 10 N）和不同的温度（23℃和37℃）下进行交联。升高NaOH浓度和温度可显著降低抗葡聚糖抗体和葡聚糖结合凝集素conconavalin A与NWs的结合。右旋糖酐免疫反应性的降低与补体组分3（补体组分3，C3）的调节作用降低以及小鼠血清中凝集素途径因子MASP-2的结合减少相关，提示交联阻断了补体的凝集素途径。小鼠腹腔巨噬细胞对NW摄取的减少与C3活化的减少有关。优化后的NWs在小鼠体内的循环半衰期长达10小时，肝脏的吸收最小，同时在血液中保持250 nm的大尺寸。我们证明了大氧化铁纳米颗粒的免疫识别可以通过化学交联-水化有效地阻断，这是一种有希望提高MRI造影剂安全性和生物惰性的策略。
One of the core issues of nanotechnology involves masking the foreignness of nanomaterials to enable in vivo longevity and long-term immune evasion. Dextran-coated superparamagnetic iron oxide nanoparticles are very effective magnetic resonance imaging (MRI) contrast agents, and strategies to prevent immune recognition are critical for their clinical translation. Here we prepared 20 kDa dextran-coated SPIO nanoworms (NWs) of 250 nm diameter and a high molar transverse relaxivity rate R2 (~400 mM−1 s−1) to study the effect of cross-linking-hydrogelation with 1-chloro-2,3-epoxypropane (epichlorohydrin) on the immune evasion both in vitro and in vivo. Cross-linking was performed in the presence of different concentrations of NaOH (0.5 to 10 N) and different temperatures (23 and 37 °C). Increasing NaOH concentration and temperature significantly decrease the binding of anti-dextran antibody and dextran-binding lectin conconavalin A to the NWs. The decrease in dextran immunoreactivity correlated with the decrease in opsonization by complement component 3 (C3) and with the decrease in the binding of the lectin pathway factor MASP-2 in mouse serum, suggesting that cross-linking blocks the lectin pathway of complement. The decrease in C3 opsonization correlated with the decrease in NW uptake by murine peritoneal macrophages. Optimized NWs demonstrated up to 10 h circulation half-life in mice and minimal uptake by the liver, while maintaining the large 250 nm size in the blood. We demonstrate that immune recognition of large iron oxide nanoparticles can be efficiently blocked by chemical cross-linking-hydrogelation, which is a promising strategy to improve safety and bioinertness of MRI contrast agents.