中文摘要：

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8.0×10-6 mol/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）。

英文摘要：

LyP-1, a cyclic nonapeptide with the function of tumor targeting, and its fluorescence labeled derivative （LyP-1-FAM） were synthesized by a solid-phase synthesis method. Functional lipid material, LyP-1-PEG 3400-DSPE, was synthesized by the specific reaction between sulfydryl and maleimide group. LyP-1-conjugated liposomes of doxorubicin （1）, fluorescein （FAM） and DiR （a near-infrared fluorescent cyanine dye） were prepared by a film hydration method, respectively. The in vitro and in vivo targeting effects and anti-tumor effects on SCI 375 melanoma cells were investigated. The results showed that the in vitro cellular uptake of LyP-1-FAM or LyP-1-conjugated liposomes loaded with FAM （LyP-1-LS/FAM） was higher than 5-FAM or common liposomes of FAM （LS/FAM）, respectively. After iv injection of LyP-1-conjugated liposomes of DiR （LyP-1-LS/DiR） or common liposomes of DiR （LS/DiR） to tumor bearing nude mice, the tumor fluorescence intensity of LyP-1-LS/DiR group was higher than LS/DiR group, which indicated that the targeting effect was improved after the modification of LyP-1. The IC50 values of LyP-1-conjugated liposomes of 1 （LyP-1-LS/1） and liposomes of 1 （LS/1） for SCI 375 cells were 3.4×10-6 and 8.0×10-6 mol/L, respectively. The tumor growth inhibition effect of LyP-1-LS/1 in tumor bearing nude mice was more significant than LS/1 （P〈0.05）.