Data Mining as a Guide for the Construction of Cross-Linked Nanoparticles with Low Immunotoxicity via Control of Polymer Chemistry and Supramolecular Assembly.
Data Mining as a Guide for the Construction of Cross-Linked Nanoparticles with Low Immunotoxicity via Control of Polymer Chemistry and Supramolecular Assembly.
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DOI：
10.1021/acs.accounts.5b00066
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发表时间：
2015-06-16
影响因子：
18.3
通讯作者：
Wooley KL
中科院分区：
文献类型：
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作者：
Elsabahy M;Wooley KL
目前正在批准或处于临床试验的不同阶段或在几个实验室中进行严格的体外和体内表征的纳米颗粒的潜在免疫毒性最近引起了特别的关注。没有明显体外或体内毒性的产品仍可能无意中触发免疫系统的各种成分，并导致严重的不良反应。细胞因子是预测生物治疗药物调节免疫系统的效果和筛选纳米颗粒免疫毒性的有用生物标志物之一，在体外和体内，并且最近被发现部分预测纳米材料的体内药代动力学和生物分布。高分子化学和超分子组装的控制为构建生物相容性纳米粒子用于生物医学临床应用提供了很大的机会。然而，收集的有关纳米材料免疫毒性的数据来源多种多样，通常使用不同的测定方法在特定条件下进行实验，因此几乎不可能进行直接比较，因此，根据现有数据调整纳米材料的特性具有挑战性。在这个帐户中，化学结构，交联，降解性，形态，浓度和表面化学对免疫毒性的聚合物纳米材料的扩展阵列的影响将突出显示，重点是使用相同的体外和体内模型和实验条件进行的测定。此外，数字描述值已被独特地用于代表纳米颗粒对细胞因子的诱导。对现有数据的这种处理提供了一种简单易行的方法来比较各种纳米材料的免疫毒性，并且发现这些值与已发表的数据相关性良好。基于本研究中所研究的聚合物系统，已经收集了有价值的信息，这些信息有助于未来设计用于生物医学应用的纳米材料，包括：a）纳米材料的免疫毒性是浓度和剂量依赖性的; B）可降解纳米颗粒的合成对于降低毒性是必不可少的; c）交联使游离聚合物链的释放最小化并保持纳米颗粒的高稳定性，从而降低其免疫毒性; e）在中性、两性离子、阴离子和阳离子纳米材料中，中性和阳离子纳米颗粒通常分别具有最低和最高的免疫毒性; f）形态、尺寸和表面化学对纳米材料与生物系统的各种组分相互作用和调节免疫系统的能力有很大影响。
The potential immunotoxicity of nanoparticles that are currently being approved or in different phases of clinical trials or under rigorous in vitro and in vivo characterizations in several laboratories has recently raised special attention. Products with no apparent in vitro or in vivo toxicity may still trigger the various components of the immune system, unintentionally, and lead to serious adverse reactions. Cytokines are one of the useful biomarkers to predict the effect of biotherapeutics on modulating the immune system and for screening the immunotoxicity of nanoparticles, both in vitro and in vivo, and were found recently to partially predict the in vivo pharmacokinetics and biodistribution of nanomaterials. Control of polymer chemistry and supramolecular assembly provides a great opportunity for construction of biocompatible nanoparticles for biomedical clinical applications. However, the sources of data collected regarding immunotoxicities of nanomaterials are diverse and experiments are usually conducted using different assays and under specific conditions, making direct comparisons nearly impossible and, thus, tailoring properties of nanomaterials based on the available data is challenging. In this account, the effects of chemical structure, crosslinking, degradability, morphology, concentration and surface chemistry on the immunotoxicity of an expansive array of polymeric nanomaterials will be highlighted, with focus being given on assays conducted using the same in vitro and in vivo models and experimental conditions. Furthermore, numerical descriptive values have been utilized, uniquely, to stand for induction of cytokines by nanoparticles. This treatment of available data provides a simple and easy way to compare the immunotoxicity of various nanomaterials, and the values were found to correlate-well with published data. Based on the investigated polymeric systems in this study, valuable information has been collected that aids in the future design of nanomaterials for biomedical applications, which include: a) Immunotoxicity of nanomaterials is concentration- and dose-dependent; b) Synthesis of degradable nanoparticles is essential to decrease toxicity; c) Crosslinking minimizes the release of free polymeric chains and maintains high stability of nanoparticles, thereby, lowering their immunotoxicity; d) Lowering amine density for cationic polymers that are being utilized for nucleic acids delivery lowers the toxicity of nanoparticles; e) Among neutral, zwitterionic, anionic and cationic nanomaterials, neutral and cationic nanoparticles usually have the lowest and highest immunotoxicity, respectively; f) Morphology, dimension and surface chemistry have a great influence on the ability of nanomaterials to interact with the various components of the biological system and to modulate the immune system.