Differential tumor cell targeting of anti-HER2 (Herceptin®) and anti-CD20 (Mabthera®) coupled nanoparticles
Differential tumor cell targeting of anti-HER2 (Herceptin®) and anti-CD20 (Mabthera®) coupled nanoparticles
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DOI：
10.1016/j.ijpharm.2006.12.002
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发表时间：
2007-03-01
影响因子：
5.8
通讯作者：
Delie, F.
中科院分区：
文献类型：
--
作者：
Cirstoiu-Hapca, A.;Bossy-Nobs, L.;Delie, F.
制备了两种类型的抗体标记纳米颗粒（mAb-NPs），目的是实现特异性肿瘤靶向。使用抗HER 2和抗CD 20单克隆抗体（mAb）作为模型配体。采用盐析法制备了平均粒径约为170 nm的聚乳酸纳米粒。此后，以两个步骤进行用mAb包被PLA NP。首先，通过两步碳二亚胺反应在PLA-NP的表面上引入巯基（-SH）。当在硫醇化反应期间使用25-1518 mol胱胺/mol PLA的胱胺浓度时，NP表面上的-SH基团的数量从150增加到400 mmol-SH/mol PLA。在第二步中，通过双功能交联剂间马来酰亚胺苯甲酰基-N-羟基-磺基琥珀酰亚胺酯（磺基-MBS）获得抗体与硫醇化NP（NPs-SH）的共价偶联。分别对于抗HER 2和抗CD 20的mAb，NP上-SH官能团的数量对与NP偶联的mAb的量没有影响。每个纳米颗粒分别共价偶联约295个抗HER 2和557个抗CD 20分子。偶联反应后的纳米颗粒尺寸约为250 nm。使用两种细胞系：SKOV-3人卵巢癌细胞（过表达HER 2）和Daudi淋巴瘤细胞（过表达CD 20），通过共聚焦显微镜测定肿瘤细胞和mAb-NP之间的特异性相互作用。结果表明，单克隆抗体-纳米粒选择性靶向过表达特异性抗原的肿瘤细胞。虽然抗CD 20标记的NP（抗CD 20 NP）结合并保留在细胞表面，但抗HER 2标记的NP（抗HER 2 NP）被有效内化。mAb-NP代表了一种有前途的方法，以提高NP在癌症治疗的主动靶向中的功效，而抗体-靶系统的选择决定了mAb-NP在与细胞结合后的命运。(c)2006 Elsevier B. V.保留所有权利。
Two types of antibody-labeled nanoparticles (mAb-NPs) were prepared with the aim to achieve specific tumor targeting. Anti-HER2 and antiCD20 monoclonal antibodies (mAb) were used as model ligands. Small poly(DL-lactic acid) nanoparticles (PLA NPs) with a mean size of about 170 nm were prepared by the salting out method. Thereafter, the coating of PLA NPs with mAbs was performed in two steps. First, thiol groups (-SH) were introduced on the surface of PLA-NPs by a two-step carbodiimide reaction. The number of -SH groups on the surface of NPs increased from 150 to 400 mmol-SH/mol PLA when cystamine concentrations of 25-1518 mol cystamine/mol PLA were used during the thiolation reaction. In the second step, covalent coupling of antibodies to thiolated NPs (NPs-SH) was obtained via a bifunctional cross-linker, m-maleimidobenzoyl-N-hydroxy-sulfosuccinimide ester (sulfo-MBS). For both mAbs anti-HER2 and anti-CD20, respectively, the number of -SH functions on the NPs had no influence on the amount of mAb coupled to the NPs. Approximately, 295 anti-HER2 and 557 anti-CD20 molecules, respectively, were covalently coupled per nanoparticle. The NPs size after the coupling reactions was about 250 nm. The specific interaction between tumor cells and mAb-NPs was determined by confocal microscopy using two cell lines: SKOV-3 human ovarian cancer cells (overexpressing HER2) and Daudi lymphoma cells (overexpressing CD20). The results showed the selective targeting of mAb-NPs to tumor cells overexpressing the specific antigen. While anti-CD20 labeled NPs (anti-CD20 NPs) bound to and remained at the cellular surface, anti-HER2 labeled NPs (anti-HER2 NPs) were efficiently internalized. The mAb-NPs represent a promising approach to improve the efficacy of NPs in active targeting for cancer therapy while the choice of the antibody-target system defines the fate of the mAb-NPs after their binding to the cells. (c) 2006 Elsevier B.V. All rights reserved.