A novel truncated basic fibroblast growth factor fragment-conjugated poly (ethylene glycol)-cholesterol amphiphilic polymeric drug delivery system for targeting to the FGFR-overexpressing tumor cells

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• 作者：Lulu Cai^a ; ¹ ; Neng Qiu^a ; ¹ ; Xia Li^a ; Kaili Luo^a ; Xiang Chen^a ; Li Yang^a ; Gu He^a ; ^{hegu@scu.edu.cn} ; Yuquan Wei^a ; Lijuan Chen^a ; ^b ; ^{lijuan17@hotmail.com}
• 关键词：Tumor-targeting drug delivery ; Chol-PEG₂₀₀₀-COOH polymer ; truncated bFGF-conjugated micelles paclitaxel
• 刊名：International Journal of Pharmaceutics
• 出版年：2011
• 出版时间：15 April 2011
• 年：2011
• 卷：408
• 期：1-2
• 页码：173-182
• 全文大小：1276 K

文摘

Targeted uptake of therapeutic nanoparticles in tumor cells-specific manner represents a potentially powerful technology in cancer therapy. In present study, we proposed a drug delivery system formulated with biocompatible and biodegradable cholesterol-block-poly (ethylene glycol) (Chol-PEG₂₀₀₀-COOH) polymer. And the surface of the polymer was chemically linked with truncated bFGF fragments (tbFGF). The tbFGF could recognize fibroblast growth factor receptors (FGFR) that are highly expressed by a variety of human cancer cells. The micelles had a size distribution of about 10–50 nm and significantly enhanced the cytotoxicity of paclitaxel to LL/2 cells as demonstrated by MTT test (IC₅₀ = 0.21 μg/mL for tbFGF conjugated Chol-PEG₂₀₀₀-COOH micelles (tbFGF-M-PTX) versus 26.43 μg/mL for free paclitaxel, respectively). Flow cytometry revealed the cellular uptake of rhodamine B encapsulated in the tbFGF-conjugated micelles was increased by 6.6-fold for HepG2, 6.2-fold for A549, 2.9-fold for C26 and 2.7-fold for LL/2 tumor cells, respectively, compared with micelles without tbFGF. The fluorescence spectroscopy images further demonstrated that the tbFGF conjugated micelles could specifically bind to the tumor cells that over-expressed FGFRs and then release rhodamine B into the cytoplasm. Our results suggest the tbFGF conjugated Chol-PEG₂₀₀₀-COOH micelles have great potential application for tumor targeting therapy.