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利用固相合成法合成了LyP-1,一种对肿瘤细胞具有靶向能力的环状九肽,及其荧光素标记物(LyP-1-FAM)。利用巯基和马来酰亚胺的专属性反应制备了功能化脂质材料LyP-1-PEG 3400-DSPE。用成膜水化法制备了LyP-1修饰的多柔比星(1)、荧光素(FAM)和近红外染料(DiR)脂质体,并评价其对SCI 375黑素瘤细胞的体内外靶向性、细胞毒性和体内抑瘤效果。体外试验表明,SCI 375细胞对LyP-1-FAM或LyP-1修饰的FAM脂质体的摄取显著高于5-FAM或普通FAM脂质体。LyP-1修饰及未修饰的DiR脂质体分别尾静脉注射给予荷瘤裸鼠后,可见LyP-1修饰组肿瘤组织的荧光强度较高,提示DiR脂质体经LyP-1修饰后体内靶向性提高。LyP-1修饰及未修饰的1脂质体在体外对SCI 375细胞的IC50分别为3.4×10-6和8.0×10-6mol/L;修饰组在荷瘤裸鼠体内的抑瘤效果也显著高于未修饰组(P<0.05)。
LyP-1, a cyclic nonapeptide with targeting ability to tumor cells, and its fluorescein label (LyP-1-FAM) were synthesized by solid-phase synthesis. The functionalized lipid material LyP-1-PEG 3400-DSPE was prepared by the specific reaction of thiol and maleimide. LyP-1-modified liposomal doxorubicin (1), fluorescein (FAM) and near infrared dye (DiR) liposomes were prepared by the membrane hydration method and their effects on the proliferation of SCI-375 melanoma cells in vitro and in vivo Targeting, cytotoxic and in vivo antitumor effects. In vitro tests showed that uptake of LyP-1-FAM or LyP-1 modified FAM liposomes by SCI 375 cells was significantly higher than that of 5-FAM or normal FAM liposomes. LyP-1 modified and unmodified DiR liposomes were injected into the tail vein of nude mice after injection, showing that the fluorescence intensity of the LyP-1 modified group was higher, suggesting that DiR liposomes modified by LyP-1 in vivo target To improve. The IC50 of LyP-1 modified and unmodified liposomes in vitro were 3.4 × 10-6 and 8.0 × 10-6mol / L for SCI375 cells, respectively. The antitumor effect of the modified group was also significant in tumor-bearing nude mice Higher than the unmodified group (P <0.05).