纳米活性炭吸附丝裂霉素C腹腔化疗的生物发光成像研究  

Intraperitoneal chemotherapy with mitomycin C bound to activated carbon nanoparticles using bioluminescence imaging technology

作　　者：张浩[1] 孙岚[1] 鄂晓[1] 曲秋莲[1] 姜爽[2] 张英鸽[1] 

机构地区：[1]军事医学科学院毒物药物研究所,国家纳米中心协作实验室,北京100850 [2]解放军210医院药理基地,辽宁大连116021

出　　处：《军事医学》2011年第4期299-302,共4页Military Medical Sciences

基　　金：国家973计划项目(2010CB933904)

摘　　要：目的用小动物生物发光成像技术(简称活体成像技术)对纳米活性炭(activated carbon nanoparticles,ACNP)吸附丝裂霉素C(mitomycin C,MMC)所组成的新型淋巴靶向制剂卡波霉素(carbomycin,CBMC)的体内抗胃癌作用进行初步评价。方法将包含有荧光素酶基因的pCIBAP-Luc载体转染人胃癌BGC-823细胞系,经G418抗性筛选获得稳定高表达荧光素酶的单克隆细胞;将持续表达荧光素酶的肿瘤细胞对6组裸鼠进行腹腔种植;1周后裸鼠腹腔形成肿瘤灶,将6组动物分别腹腔给予生理盐水、ACNP、MMC、CBMC低剂量、CBMC中剂量和CBMC高剂量药物。分别于给药后7,14,21 d用IVIS活体成像系统动态监测肿瘤生长情况。结果体外影像结果显示,表达荧光素酶的细胞数量与其发光强度呈正相关;裸鼠活体成像结果显示,成功建立了高表达荧光素酶的腹腔胃癌移植模型;MMC组和3个剂量的CBMC组均较生理盐水组显著抑制肿瘤的生长;单独使用ACNP没有抗肿瘤作用;在含相同MMC药量的情况下,与MMC组相比,CBMC组能够显著抑制肿瘤的生长。结论活体成像技术可动态监测胃癌腹腔肿瘤灶的生长发展过程,是评价抗肿瘤药物CBMC的一种新的有效手段;CBMC裸鼠腹腔化疗能有效抑制胃癌细胞的生长,具有良好的临床应用前景。Objective To prepare a new drug delivery system,carbomycin（CBMC）,composed of activated carbon nanoparticles（ACNP） adsorbing mitomycin C（MMC） for lymphatic targeting intraperitoneal chemotherapy,and to evaluate its beneficial effects in vivo using bioluminescence imaging technology.Methods Human gastric carcinoma cell line BGC-823 cells were transfected with plasmids pCIBAP-Luc.Resistant clones were screened using G418.Those clones were chosen that expressed luciferase in vitro using bioluminescence imaging technology.Those stably transfected monoclones were intraperitoneally transplanted into nude mice and tumorigenesis was observed using bioluminescence imaging seven days later.Next,these mice were divided into six groups and given different dose of medicine.The tumor in vivo was monitored by whole-body images.Results In vitro results showed that the photon emission was correlated with the increase of the cell number.In vivo results indicated the successful establishment of the model of BGC-823-Luc tumor in abdominal cavity.MMC group and three CBMC groups all indicated that the growth of tumor was prohibited.ACNP could not prohibit the growth of tumor.Used at the same dose as MMC,CBMC was better than MMC in preventing the growth of gastric carcinoma in vivo.Conclusion The study provides a platform for monitoring the tumor in abdominal cavity and evaluating the efficacy of anti-tumor drugs in vivo.CBMC holds a good promise of clinical use due to its advantages such as high selectivity and low toxicity.

关 键 词：生物发光成像 纳米活性炭 丝裂霉素C 腹腔化疗 

分 类 号：R735.2[医药卫生—肿瘤]