文献：Synthesis and Evaluation of a Novel Lipophilic Folate Receptor Targeting Ligand

作者：YING LIU, SONGLIN XU, LESHENG TENG, BRYANT YUNG, JING ZHU, HONG DING and ROBERT J. LEE

文献链接：https://ar.iiarjournals.org/content/31/5/1521.short

摘要：

Background: Folate receptor (FR)-targeted liposomes have been investigated as delivery vehicles for anticancer drugs. A novel lipophilic FR ligand, folate-glutathione-polyethyleneglycol-distearoyl phosphatidylethanolamine (F-GSH-PEG-DSPE), was synthesized, incorporated into liposomes and evaluated for FR targeting efficiency. These liposomes were then evaluated as carriers of the chemotherapy agent vincristine (VIN). Materials and Methods: F-GSH-PEG-DSPE was synthesized and FR-targeted liposomes loaded with either calcein (F-L-Calcein) or VIN (F-L-VIN) were prepared by thin film hydration followed by polycarbonate membrane extrusion and, in the case of VIN, by remote loading. To assess liposome stability, the uptake of F-L-VIN in KB (FR+) cancer cells was measured after storage under 4°C for 3 months. Comparative pharmacokinetic studies were carried out with F-L-VIN and L-VIN (non-targeted control liposomes). Results: F-L-Calcein showed significantly higher cellular uptake in KB cells compared to non-targeted liposomes. In addition, F-L-VIN showed enhanced cytotoxicity in KB cells in vitro compared to control liposomes. Pharmacokinetic parameters indicated that both F-L-VIN and control liposomes had higher area under the curve (AUC), mean residence time (MRT), elimination half life (t1/2-β) and lower total body clearance (CL) than those of free VIN, while there were no significant differences between these liposomal formulations. Conclusion: F-GSH-PEG-DSPE is effective as a novel ligand for the synthesis of FR-targeted liposomes.

合成了一种新型亲脂性FR配体，叶酸-谷胱甘肽聚乙二醇二硬脂酰磷脂酰乙醇胺（F-GSH-PEG-DSPE），将其掺入脂质体中，并评估了FR靶向效率。然后将这些脂质体作为化疗药物长春新碱（VIN）的载体进行评估。

材料和方法：合成F-GSH-PEG-DSPE，通过薄膜水合、聚碳酸酯膜挤出和远程加载制备负载钙黄绿素（F-L-calcein）或VIN（F-L-VIN）的FR靶向脂质体。

为了评估脂质体的稳定性，在4°C下储存3个月后，测量KB（FR+）细胞对F-L-VIN的摄取。用F-L-VIN和L-VIN（非靶向对照脂质体）进行了比较药代动力学研究。

结果：与非靶向脂质体相比，F-L-Calcein在KB细胞中的细胞摄取明显更高。此外，与对照脂质体相比，F-L-VIN在体外KB细胞中显示出增强的细胞毒性。

药代动力学参数表明，F-L-VIN和对照脂质体的曲线下面积（AUC）、平均停留时间（MRT）、消除半衰期（t1/2-β）和全身清除率（CL）均高于游离VIN，但这些脂质体制剂之间没有显著差异。

结论：F-GSH-PEG-DSPE作为合成FR靶向脂质体的新型配体是有效的。

相关推荐：

DSPE-PEG-Biotin

DSPE-PEG-Boronate

DSPE-PEG-CH2COOH

DSPE-PEG-COOH

DSPE-PEG-Cy3

DSPE-PEG-Cy5

DSPE-PEG-DBCO

DSPE-PEG-FITC

DSPE-PEG-Folate

DSPE-PEG-IA

DSPE-PEG-Mal

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