摘要
目的对于Cyclo[Arg-Gly-Asp-D-Phe-Lys(Ac-CH_2-SH)](RGD)与R8肽共修饰麦角甾醇联合顺铂脂质体递药系统进行裸鼠体内靶向性及抗肺癌作用初步评价。方法第一步,对造模成功的A549荷瘤裸鼠尾静脉注射包封有近红外DiR荧光染料的RGD环肽与R8肽修饰、单一RGD环肽修饰、单一R8肽修饰、不修饰麦角甾醇联合顺铂脂质体,在小动物活体成像仪下不同时间点下观察脂质体的体内分布并评价其靶向性。第二步,连续给药14 d,观测小鼠体重、肿瘤生长情况,于第14天处死动物,取血,并摘取各小鼠瘤组织、脾脏、肺组织,以瘤重、抑瘤率、血清转化生长因子-β1(TGF-β1)、组织金属蛋白酶抑制剂(TIMPs)、肿瘤坏死因子-α(TNF-α)水平、脾脏指数、瘤组织及肺脏的病理组织改变为指标,初步评价各脂质体在小鼠体内的抑瘤作用。结果靶向性结果表明,RGD与R8共修饰脂质体在荷瘤裸鼠肿瘤部位的荧光强度最高,高浓度下靶向性最为明显,其他几组的靶向作用均较弱。初步药效学结果表明,各给药组对于小鼠体重无明显变化,RGD与R8共修饰脂质体高、中剂量组有明显抑瘤作用,其中,高剂量组抑瘤作用最为显著,且血清中高表达TNF-α细胞因子,RGD与R8共修饰脂质体中、低剂量组脾脏指数较阳性药组显著升高。结论 RGD环肽与R8肽共修饰麦角甾醇联合顺铂靶向脂质体递药系统,进一步提高了体内肿瘤靶向性及抗肺癌作用。
OBJECTIVE To preliminarily evaluate the targeting and anti-lung cancer effect in vivo in nude mice induced by Cyclo[Arg-Gly Asp-D-Phe-Lys(Ac-CH2-SH)](RGD) and R8 peptides modified ergosterol combined cisplatin liposomes. METHODS The first step, injected RGD cyclo peptide and R8 peptide-modified, single modified or no modified ergosterol combined cisplatin liposome in the caudal vein of nude mouse bearing the tumor, the body distribution and targeting of each group under the different time points through small animals living imager were observed. The second step, continuously, dose every other day for 14 d, observating the weight of mice and the tumor growth situation. The animals were drawed blood and then were put to death, removing the tumor, the spleen and the lung tissue of all the mice. As the index of the tumor weight, the tumor suppression effect, the level of TGF-β1, TIMPs and TNF-α in serum, the spleen index and changes of the tumor and lung tissue, investigate the tumor suppression effect in mice of the liposomes preliminary. RESULTS The targeting result of tumor-bearing nude mice displays that the fluorescence intensity of RGD and R8 peptides-modified liposome is the highest and the targeting is most obvious under high concentration and other group of liposome are weaker. Preliminary pharmacodynamics results show that each dosage group of mice have no obvious change in body weight and the high and middle dose group of RGD and R8 peptides-modified liposomes has tumor suppression effect obviously. The high dose group of RGD and R8 peptides-modified liposome is the most significant. It has high expression of cytokines (TNF-α) in serum. The spleen index of middle and low dose group of RGD and R8 peptides-modified liposomes significantly increased compared with positive medicine group. CONCLUSION RGD cyclo peptide and R8 peptide-modified ergosterol combined cisplatin targeting liposome drug delivery system further improves the tumor targeting and anti-lung cancer effect in vivo.
作者
王娟
米完完
应园园
王航利
张梦迪
黄绳武
WANG Juan;MI Wan-wan;YING Yuan-yuan;WANG Hang-li;ZHANG Meng-di;HUANG Sheng-wu(College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou 310053, China)
出处
《中国药学杂志》
CAS
CSCD
北大核心
2019年第5期364-372,共9页
Chinese Pharmaceutical Journal
基金
国家自然科学基金项目资助(81473361)
浙江省自然科学基金项目资助(LY16H280010)
作者简介
王娟,女,硕士,研究方向:药物新剂型与新技术;通讯作者:黄绳武,男,教授,研究方向:药物新剂型与新技术,Tel:(0571)86613524,E-mail:hsw55@163.com.
