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          mPEG-DSPE修飾脂質體在靶向遞送和免疫逃逸中的應用探索
          發(fā)布時間:2025-07-10     作者:zyl   分享到:

          文獻:Optimization of tumor-selective targeting by basic fibroblast growth factor-binding peptide grafted PEGylated liposomes

          作者:Takeshi Terada, Miki Mizobata, Shigeru Kawakami, Fumiyoshi Yamashita, Mitsuru Hashida

          文獻鏈接:https://www.sciencedirect.com/science/article/abs/pii/S0168365907000703

          摘要:

          KRTGQYKLC (bFGF), is recognized by fibroblast growth factor (FGF) receptor (FGFR) via binding to basic FGF (bFGF), and is capable of being used for drug delivery to tumors highly expressing FGFR and bFGF. However, although the binding and uptake of the liposomes (bFGFp-liposomes) modified by the peptide increased in the presence of bFGF, the modification induced non-specific uptake. To overcome this problem, here, we prepared bFGFp-liposomes including mPEG-DSPE. The 5 and 10% mPEG5000/ and 10% mPEG3000/bFGFp-liposomes reduced most of the interaction with erythrocytes and the uptake by macrophages, suggesting the sustained blood circulation of bFGFp grafted PEGylated liposomes. Furthermore, 10% mPEG3000/bFGFp-liposomes produced a significant increase in uptake in NIH3T3, A549, and B16BL6 cells with the expression of FGFR following pre-incubation with bFGF, but no increase in CHO-K1 cells lacking FGFR expression. Taken together, these results lead us to believe that bFGFp grafted PEGylated liposomes possess the functions of both PEGylated stealth liposomes and the tumor-targeting liposomes. 

          Gso6k8KkkM7RycDaQNRv.png

          肽KRTGQYKLC(bFGF)通過與堿性FGF(bFGF)結合被成纖維細胞生長因子(FGF)受體(FGFR)識別,并且能夠用于向高表達FGFR和bFGF的腫瘤遞送藥物。

          然而,盡管在bFGF存在下,肽修飾的脂質體(bFGFp脂質體)的結合和攝取增加,但這種修飾誘導了非特異性攝取。為了克服這個問題,我們在這里制備了含有mPEG-DSPE的bFGFp脂質體。

          5%mPEG5000/和10%mPEG3000/bFGFp脂質體減少了與紅細胞的大部分相互作用和巨噬細胞的攝取,表明bFGFp接枝PEG化脂質體的持續(xù)血液循環(huán)。

          此外,10%mPEG3000/bFGFp脂質體在與bFGF預孵育后,在表達FGFR的NIH3T3、A549和B16BL6細胞中顯著增加了攝取,但在缺乏FGFR表達的CHO-K1細胞中沒有增加。

          綜上所述,這些結果使我們相信bFGFp接枝的PEG化脂質體具有PEG化隱形脂質體和腫瘤靶向脂質體的功能。

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