Targetability of novel immunoliposomes prepared by a new antibody conjugation technique
Targetability of novel immunoliposomes prepared by a new antibody conjugation technique
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DOI：
10.1016/s0378-5173(99)00002-2
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发表时间：
1999-04-20
影响因子：
5.8
通讯作者：
Rothe, U
中科院分区：
文献类型：
--
作者：
Bendas, G;Krause, A;Rothe, U
In order to develop long-circulating immunoliposomes (IL), which combine sterical stabilization with a superior targetability, we have introduced a new methodology for attaching monoclonal antibodies direcry onto the distal ends of liposome-grafted polyethylene glycol (PEG) chains. Therefore, we have synthesized a new PEG-PE derivative, which had been endgroup-functionalized with cyanuric chloride. Antibodies can simply be coupled to this membrane anchor in mild basic conditions (pH 8.8) without the need for previous antibody derivatizations. The coupling results have been determined with consideration to various liposome parameters and have been compared to several established antibody coupling procedures, where antibodies had been linked directly to the liposome surface in the presence of PEG (conventional IL). To investigate the targetability of the resulting new IL, anti E-selectin mAb have been coupled and the degree of binding selectin-containing cells has been analyzed. The terminal coupled antibodies show a 1.8-fold higher degree of in vitro cell binding compared to conventional IL, which has been attributed to the antibody position being more easy accessible at the PEG termini. Furthermore, we have illustrated the liposome surface topology and the coupled antibodies by atomic force microscopy, which for such fluid IL has been used first. These images have finely corresponded to the cell binding results, and have been discussed in terms of antibody position and flexibility at the liposome surface. (C) 1999 Elsevier Science B.V. All rights reserved.
