Synthetic nano-LDL with paclitaxel oleate as a targeted drug delivery vehicle for glioblastoma multiforme
Synthetic nano-LDL with paclitaxel oleate as a targeted drug delivery vehicle for glioblastoma multiforme
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DOI：
10.1016/j.jconrel.2007.09.007
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发表时间：
2007-12-20
影响因子：
10.8
通讯作者：
Forte, Trudy M.
中科院分区：
文献类型：
--
作者：
Nikanjarn, Mina;Gibbs, Andrew R.;Forte, Trudy M.
低密度脂蛋白（LDL）受体已被证明是上调GBM肿瘤细胞在体外，因此是一个潜在的分子靶向治疗剂的交付。通过将亲脂性前药紫杉醇油酸酯掺入到合成的纳米LDL（nLDL）颗粒中，将其开发为靶向GBM细胞的药物递送载体。通过将含有脂质结合基序和载脂蛋白13100的LDL受体（LDLR）结合结构域的合成肽与由磷脂酰胆碱、三油酸甘油酯和紫杉醇油酸酯组成的脂肪乳剂组合，构建含有紫杉醇油酸酯（nLDL-PO）的纳米LDL。将油酸紫杉醇掺入脂质颗粒的核心中。发现GBM细胞系中的nLDL-PO细胞存活具有时间、浓度和细胞系依赖性。在短时间药物孵育下观察到细胞杀伤，并在6 h时表现出饱和。在LDL受体抑制剂苏拉明存在下，nLDL-PO细胞存活率提高，表明药物通过LDL受体递送。总的来说，这些数据强烈表明合成的纳米LDL可以掺入亲脂性药物，并且能够杀死GBM细胞。nLDL-PO具有作为通过LDL受体靶向GBM肿瘤的选择性药物递送载体的潜力。(c)2007 Elsevier B. V.保留所有权利。
The low density lipoprotein (LDL) receptor has been shown to be upregulated in GBM tumor cells in vitro and is therefore a potential molecular target for the delivery of therapeutic agents. A synthetic nano-LDL (nLDL) particle was developed as a drug delivery vehicle targeted to GBM cells by incorporating a lipophilic prodrug, paclitaxel oleate, into the particle. Nano-LDL containing paclitaxel oleate (nLDL-PO) was constructed by combining a synthetic peptide containing a lipid binding motif and the LDL receptor (LDLR) binding domain of apolipoprotein 13100 with a lipid emulsion consisting of phosphatidyl choline, triolein, and paclitaxel oleate. Paclitaxel oleate incorporated into the core of the lipid particle. nLDL-PO cell survival in GBM cell lines was found to be time, concentration, and cell line dependent. Cell killing was observed with short drug incubations and exhibited saturation at 6 h. nLDL-PO cell survival improved in the presence of the LDL receptor inhibitor, suramin, demonstrating that the drug was delivered via the LDL receptor. Collectively, these data strongly suggest that the synthetic nano-LDLs can incorporate lipophilic drugs and are capable of killing GBM cells. nLDL-PO has the potential to serve as a selective drug delivery vehicle for targeting GBM tumors via the LDL receptor. (c) 2007 Elsevier B.V. All rights reserved.