文獻：流動條件下可生物降解微球與細胞因子激活內皮細胞的特異性粘附

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

作者：達拉爾，米林德·K

節選：

抽象的

在多種疾病環境中，各種內皮細胞粘附分子 (ECAM) 的表達似乎會增加，這使得這些分子成為定向藥物遞送方案的有吸引力的靶點。一種方法是使用帶有 mAb 的聚合物可生物降解微球來靶向表達增加的 ECAM。我們利用生物素-親和素化學方法將 mAb 與 E-選擇素或 ICAM-1 偶聯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。我們測試了所得 mAb 包被的可生物降解顆粒與人臍靜脈內皮細胞 (HUVEC) 的粘附性。我們發現，mAb 包被的 PLA-PEG-生物素微球對 4 小時后 E-選擇素和 ICAM-1 表達水平較高的 IL-1β 激活的 HUVEC 的粘附性高于對不表達 E-選擇素且 ICAM-1 表達水平較低的未激活 HUVEC 的粘附性。我們還發現粘附力依賴于剪切應力。此外，我們發現*E-選擇素包被微球對4小時IL-1β激活的HUVEC的選擇性與用于生成*E-選擇素包被微球的*E-選擇素濃度密切相關。這些結果表明，包被有*ECAM單克隆*體的PLA-PEG-生物素顆粒可用于選擇性地將藥物靶向炎癥部位的內皮細胞。

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.

西安齊岳生物提供相關產品：

mPEG-PLA

PLA-PEG-SC

FA-PEG-PLA

Mal-NH-PEG-PLA

Mal-PEG-PLA

Galactose-PEG-PLA

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