叶酸靶向顺铂聚合物胶束对肺癌细胞SPC-A-1的毒性和辐射增敏作用  

Folate-functionalized and cisplatin loaded polymeric micelles combined with concurrent radiotherapy for the treatment of lung cancer in vitro and in vivo

作　　者：黄宇翔[1] 王萱怡[1] 刘永彪[1] 吴银霞[1] 杨航[1] 姚志峰[1] 徐国平[1] 

机构地区：[1]南京医科大学第一附属医院放疗科,南京210029

出　　处：《辐射研究与辐射工艺学报》2012年第4期231-236,共6页Journal of Radiation Research and Radiation Processing

基　　金：国家自然科学基金(30870741);江苏省自然科学基金(BK2007245)资助

摘　　要：以顺铂为对照,使用具有叶酸靶向基团的聚乙二醇枝接聚天冬氨酸聚合物胶束顺铂载体FA-PEG-g-PAsp-CDDP和无叶酸靶向基团的mPEG-g-PAsp-CDDP,通过比较这3种药物对肺癌细胞SPC-A-1体外的细胞毒性以及单独用药和同步放疗对裸鼠移植瘤的生长抑制作用,验证FA-PEG-g-PAsp-CDDP的肿瘤抑制和辐射增敏效果。在体外CCK-8实验中比较顺铂、FA-PEG-g-PAsp-CDDP和mPEG-g-PAsp-CDDP对过表达叶酸受体的肺癌细胞株SPC-A-1的细胞毒性作用,在体内试验中比较顺铂、FA-PEG-g-PAsp-CDDP和mPEG-g-PAsp-CDDP单独用药和同步放疗对裸鼠移植瘤的生长抑制及放射增敏作用,并观察对裸鼠体重的影响。结果显示:含过量叶酸的普通培养基中FA-PEG-g-PAsp-CDDP和mPEG-g-PAsp-CDDP的细胞毒性作用相似,而在不含叶酸培养基中FA-PEG-g-PAsp-CDDP的细胞毒性高于mPEG-g-PAsp-CDDP,IC50约为后者的1/(3p<0.05)。单独用药实验中FA-PEG-g-PAsp-CDDP和CDDP体内抑瘤效果无统计学差异(p>0.05),但均高于mPEG-g-PAsp-CDDP组和空白对照组(p<0.05);同步放化疗实验中FA-PEG-g-PAsp-CDDP的抑瘤效果优于CDDP(p<0.05),并且两者均优于mPEG-g-PAsp-CDDP组和单独放疗组(p<0.05)。裸鼠CDDP给药后体重下降明显,最多下降约10%,而FA-PEG-g-PAsp-CDDP和mPEG-g-PAsp-CDDP组裸鼠体重无明显下降。FA-PEG-g-PAsp-CDDP能有效抑制肿瘤生长,叶酸靶向基团增强了其对过表达叶酸受体肿瘤的抑制作用,并且较CDDP有更强的放射增敏效果和更低的毒副作用。The tumor-targeting drug delivery system FA-PEG-g-PAsp-CDDP micelles were fabricated from folate-conjugated PEG-graft-α, β-poly [（N-aminoacidyl）-aspartamide] and CDDP. The purpose of this experiment was to test the anti-tumor and radio-sensitizing efficiency of FA-PEG-g-PAsp-CDDP in vitro and in vivo. In vitro, we compared the cytotoxicity of FA-PEG-g-PAsp-CDDP, mPEG-g-PAsp-CDDP and CDDP in the FR over-expressing cell lines SPC-A-1 by CCK-8 test. In vivo, we compared their anti-tumor efficiency in tumor-bearing nude mice when the drugs were administered along or concurrent with radiation. The body weight change was also observed. The re- sults showed that in normal culture medium which contained over-dose folate, FA-PEG-g-PAsp-CDDP and mPEG-g-PAsp-CDDP had the same cytotoxicity, but it in folate-free culture medium, IC50 of FA-PEG-g-PAsp-CDDP was only about 1/3 of that in mPEG-g-PAsp-CDDP （p0.05）. When administered along, the anti-tumor efficiency of FA-PEG-g-PAsp-CDDP and CDDP had no difference （p0.05）, but both were higher than mPEG-g-PAsp-CDDP and blank control （p0.05）. When concurrent with radiation, the anti-tumor efficiency of FA-PEG-g-PAsp-CDDP was higher than that of CDDP （p0.05）, and both were higher than that of mPEG-g-PAsp-CDDP and radiation alone （p0.05）. The body weight of nude mice was decreased by about 10% in CDDP group, but had no change in FA-PEG-g-PAsp-CDDP and mPEG-g-PAsp-CDDP groups. In conclusion, FA-PEG-g-PAsp-CDDP could inhibit the growth of tumors effectively. The folate receptor targeting group enhanced the anti-tumor efficiency of the micelles in FR over-expressing tumor. And FA-PEG-g-PAsp-CDDP has greater radio-sensitization effect and low toxicity than that of CDDP.

关 键 词：顺铂 叶酸 聚合物胶束 肿瘤靶向 放疗 肺癌细胞 

分 类 号：R734.2[医药卫生—肿瘤] R730.55[医药卫生—临床医学]