文献：流动条件下可生物降解微球与细胞因子激活内皮细胞的特异性粘附

链接：https://etd.ohiolink.edu/acprod/odb_etd/etd/r/1501/10?clear=10&p10_accession_num=ohiou1040071303

作者：达拉尔，米林德·K

节选：

抽象的

在多种疾病环境中，各种内皮细胞粘附分子 (ECAM) 的表达似乎会增加，这使得这些分子成为定向药物递送方案的有吸引力的靶点。一种方法是使用带有 mAb 的聚合物可生物降解微球来靶向表达增加的 ECAM。我们利用生物素-亲和素化学方法将 mAb 与 E-选择素或 ICAM-1 偶联到由生物素化的聚乳酸-聚乙二醇 (PLA-PEG-生物素) 共聚物制成的微球上。我们测试了所得 mAb 包被的可生物降解颗粒与人脐静脉内皮细胞 (HUVEC) 的粘附性。我们发现，mAb 包被的 PLA-PEG-生物素微球对 4 小时后 E-选择素和 ICAM-1 表达水平较高的 IL-1β 激活的 HUVEC 的粘附性高于对不表达 E-选择素且 ICAM-1 表达水平较低的未激活 HUVEC 的粘附性。我们还发现粘附力依赖于剪切应力。此外，我们发现*E-选择素包被微球对4小时IL-1β激活的HUVEC的选择性与用于生成*E-选择素包被微球的*E-选择素浓度密切相关。这些结果表明，包被有*ECAM单克隆*体的PLA-PEG-生物素颗粒可用于选择性地将药物靶向炎症部位的内皮细胞。

Abstract

In a variety of disease settings the expression of various endothelial cell adhesion molecules (ECAMs) appears to be increased, making these molecules attractive targets for directed drug delivery schemes. One approach is to use polymeric biodegradable microspheres bearing a mAb for an ECAM whose expression is increased. We used biotin-avidin chemistry to couple a mAb to E-selectin or ICAM-1 to microspheres made from a biotinylated poly (lactic acid) poly (ethylene glycol) (PLA-PEG-biotin) copolymer. We tested the adhesion of the resulting mAb coated biodegradable particles to human umbilical vein endothelial cells (HUVEC). We found that the mAb coated PLA-PEG-biotin microspheres show high specific adhesion to 4 hr. IL-1β activated HUVEC expressing high levels of E-selectin and ICAM-1 relative to the level of adhesion to unactivated HUVEC that express no E-selectin and a low level of ICAM-1. We also found that the adhesion was shear stress dependent. Additionally, we have found that the selectivity of anti-E-selectin coated microspheres to 4 hr. IL-1β activated HUVEC is a strong function of the concentration of anti-E-selectin used to generate the anti-E-selectin coated microspheres. These results suggest that PLA-PEG-biotin particles coated with mAbs to ECAMs could be used to selectively target drugs to endothelium present at sites of inflammation.

西安齐岳生物提供相关产品：

mPEG-PLA

PLA-PEG-SC

FA-PEG-PLA

Mal-NH-PEG-PLA

Mal-PEG-PLA

Galactose-PEG-PLA

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