Basic fibroblast growth factor-binding peptide as a novel targeting ligand of drug carrier to tumor cells
Basic fibroblast growth factor-binding peptide as a novel targeting ligand of drug carrier to tumor cells
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DOI：
10.1080/10611860600849498
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发表时间：
2006-09-01
影响因子：
4.5
通讯作者：
Hashida, Mitsuru
中科院分区：
文献类型：
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作者：
Terada, Takeshi;Mizobata, Miki;Hashida, Mitsuru
利用碱性成纤维细胞生长因子（bFGF）靶向肿瘤细胞的药物系统已被广泛报道。在这项研究中，肽KRTGQYKLC（bFGF 0），含有半胱氨酸的bFGF衍生肽的羧基末端，被用作一种新的配体靶向肿瘤细胞。将bFGF β与牛血清白蛋白（BSA）和脂质体缀合。该肽显示出抑制bFGF与FGF受体-1（FGFR 1）的结合。有趣的是，使用表面等离子体共振（SPR）测定的结合研究揭示了bFGFi 3-BSA不与FGFR 1结合，而是选择性地与bFGF结合。此外，SPR测定表明，bFGF预处理后，bFGFi 3-BSA能够与FGFR 1结合。共聚焦显微镜研究表明，bFGF预处理显著增强了高表达FGFRs的NIH 3 T3细胞对bFGFp-BSA的摄取。然后，通过马来酰亚胺-PEG-PE与bFGF β偶联，制备了含bFGF β的PEG化脂质体（bFGF β脂质体）.经bFGF预处理后，NIH 3 T3细胞对bFGF β-脂质体的摄取显著增强。这些结果表明，bFGF β-BSA和bFGF β脂质体通过与bFGF结合而被NIH 3 T3细胞摄取。bFGF β-BSA和bFGF β-脂质体对NIH 3 T3细胞增殖无明显影响。该策略可用作靶向高度表达FGFR而无增殖效应的肿瘤的新系统。
Drug systems targeting tumor cells using basic fibroblast growth factor ( bFGF) have been widely reported. In this study, the peptide KRTGQYKLC ( bFGFp), containing cysteine at the carboxyl termination of the bFGF-derived peptide, was applied as a novel ligand targeting tumor cells. bFGFp was conjugated with bovine serum albumin ( BSA) and liposomes. The peptide was shown to inhibit the binding of bFGF to FGF receptor-1 (FGFR1). Interestingly, the binding study using surface plasmon resonance (SPR) assay revealed that the bFGFp-BSA was not bound to FGFR1, but was selectively bound to bFGF. Furthermore, the SPR assay showed that bFGFp-BSA is capable of binding to FGFR1 following the pretreatment with bFGF. The confocal microscopy study indicated that the uptake of bFGFp-BSA by NIH3T3 cells, which highly express FGFRs, was significantly enhanced by pretreatment with bFGF. Then, PEGylated liposomes containing bFGFp (bFGFp liposome) were prepared by conjugating maleimide- PEG- PE with bFGFp. Following the pretreatment of bFGF, the uptake of bFGFp-liposomes by NIH3T3 cells was significantly enhanced. These results suggest that bFGFp-BSA and bFGFp liposomes are taken by NIH3T3 cells via binding with bFGF. In addition, both bFGFp-BSA and bFGFp-liposomes had no effect on the proliferation of NIH3T3 cells. This strategy can be used as a novel system for targeting tumors highly expressing FGFRs without a proliferation effect.