Targeting cancer cells using PLGA nanoparticles surface modified with monoclonal antibody
Targeting cancer cells using PLGA nanoparticles surface modified with monoclonal antibody
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DOI：
10.1016/j.jconrel.2007.03.012
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发表时间：
2007-07-13
影响因子：
10.8
通讯作者：
Kristl, Julijana
中科院分区：
文献类型：
--
作者：
Kocbek, Petra;Obermajer, Natasa;Kristl, Julijana
将药物靶向其作用部位仍然是药物研究的主要挑战。在这项研究中，聚乳酸-羟基乙酸共聚物（PLGA）免疫纳米粒子的制备靶向浸润性上皮性乳腺肿瘤细胞。单克隆抗体（mAb）被用作归巢配体，并以共价或非共价方式连接到纳米颗粒表面。对mAb在纳米粒子表面的存在、稳定性和识别性能进行了测试。蛋白质测定，表面等离子体共振，流式细胞术和荧光免疫染色证实了在这两种情况下的纳米颗粒上的mAb的存在。然而，使用细胞裂解物的结合试验显示，仅对于吸附了mAb的纳米颗粒保留了识别特性。这些纳米颗粒比未涂覆的纳米颗粒更可能与靶细胞结合。两种类型的纳米颗粒进入单一培养物中的靶MCF-IOA neoT细胞。在MCF-IOA neoT和Caco-2细胞的共培养中，免疫纳米颗粒仅定位于MCF-IOA neoT细胞，而未涂覆的纳米颗粒随机分布。免疫纳米颗粒仅进入MCF-IOA neoT细胞，而未包被的纳米颗粒被两种细胞类型摄取，表明免疫纳米颗粒的特异性靶向。总之，我们证明了一种方法，通过该方法可以将单克隆抗体结合到纳米颗粒上，而不会损害其靶向能力。此外，结果显示了新载体系统将小或大活性物质靶向递送到感兴趣的细胞或组织中的有效性。(C)2007 Elsevier B. V.保留所有权利。
Targeting drugs to their sites of action is still a major challenge in pharmaceutical research. In this study, polylactic-co-glycolic acid (PLGA) immuno-nanoparticles were prepared for targeting invasive epithelial breast tumour cells. Monoclonal antibody (mAb) was used as a homing ligand and was attached to the nanoparticle surface either covalently or non-covalently. The presence of mAb on the natioparticle surface, its stability and recognition properties were tested. Protein assay, surface plasmon resonance, flow cytometry and fluorescence-immunostaining confirmed the presence of mAb on nanoparticles in both cases. However, a binding assay using cell lysate revealed that the recognition proper-ties were preserved only for nanoparticles with adsorbed mAb. These nanoparticles were more likely to be bound to the targeted cells than non-coated nanoparticles. Both types of nanoparticles entered the target MCF- I OA neoT cells in mono-culture. In co-culture of MCF- I OA neoT and Caco-2 cells immuno-nanoparticles were localized solely to MCF- I OA neoT cells, whereas non-coated nanoparticles were distributed randomly. Immunonanoparticles entered only MCF- I OA neoT cells, while non-coated nanoparticles were taken up by both cell types, indicating specific targeting of the immuno-nanoparticles. In conclusion, we demonstrate a method by which mAbs can be bound to nanoparticles without detriment to their targeting ability. Furthermore, the results show the effectiveness of the new carrier system for targeted delivery of small or large active substances into cells or tissues of interest. (C) 2007 Elsevier B.V. All rights reserved.