Immunocompatibility properties of lipid-polymer hybrid nanoparticles with heterogeneous surface functional groups.

Immunocompatibility properties of lipid-polymer hybrid nanoparticles with heterogeneous surface functional groups.
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DOI:
10.1016/j.biomaterials.2009.01.005
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发表时间:
2009-04
期刊:
影响因子:
14
通讯作者:
Farokhzad, Omid C.
Farokhzad, Omid C.
中科院分区:
工程技术1区
文献类型:
--
作者:
Salvador-Morales, Carolina;Zhang, Liangfang;Langer, Robert;Farokhzad, Omid C.

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在此我们报道了脂质 - 聚合物杂化纳米粒子(NPs)的免疫学特性,并提出了一种控制这些纳米粒子诱导的补体激活水平的方法。该方法包括用甲氧基、羧基和氨基对纳米粒子表面进行高度特异性修饰。具有甲氧基表面基团的杂化纳米粒子诱导的补体激活最低,而具有氨基表面基团的纳米粒子诱导的激活最高。羧基、氨基和甲氧基之间的所有可能组合也在一定程度上激活了补体系统。所有类型的纳米粒子主要通过替代途径而非凝集素途径激活补体系统。具有羧基和氨基表面基团的纳米粒子在很小程度上激活了经典途径。人血清和血浆蛋白结合研究表明,这些纳米粒子具有不同的蛋白结合模式。对补体激活和凝血激活的研究表明,具有甲氧基表面基团的纳米粒子可能是药物递送应用的理想候选者,因为它们不太可能在人体内引起任何免疫不良反应。
Here we report the immunological characterization of lipid-polymer hybrid nanoparticles (NPs) and propose a method to control the levels of complement activation induced by these NPs. This method consists of the highly specific modification of the NP surface with methoxyl, carboxyl, and amine groups. Hybrid NPs with methoxyl surface groups induced the lowest complement activation, whereas the NPs with amine surface groups induced the highest activation. All possible combinations among carboxyl, amine, and methoxyl groups also activated the complement system to a certain extent. All types of NPs activated the complement system primarily via the alternative pathway rather than the lectin pathway The classical pathway was activated to a very small extent by the NPs with carboxyl and amine surface groups. Human serum and plasma protein binding studies showed that these NPs had different protein binding patterns. Studies of both complement activation and coagulation activation suggested that NPs with methoxyl surface groups might be an ideal candidate for drug delivery applications, since they are not likely to cause any immunological adverse reaction in the human body.
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