Chemotherapy for gastric cancer by finely tailoring anti-Her2 anchored dual targeting immunomicelles
Chemotherapy for gastric cancer by finely tailoring anti-Her2 anchored dual targeting immunomicelles
复制标题
通过精细定制抗 Her2 锚定双靶向免疫胶束进行胃癌化疗。
DOI：
10.1016/j.biomaterials.2012.04.016
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发表时间：
2012-07-01
期刊：
影响因子：
14
通讯作者：
Guo, Yajun
中科院分区：
文献类型：
--
作者：
Li, Wei;Zhao, He;Guo, Yajun
具有高体内血清稳定性和静脉内（i. v.）注射对于促进化疗是非常需要。在此，我们精细地合成并定制了定义明确的抗Her 2抗体Fab片段缀合的免疫胶束（FCIMs），其显示出有趣的双重靶向功能。具有体积相变温度（VPTT：39 ℃）的热敏性聚（N-异丙基丙烯酰胺-共-N，N-二甲基丙烯酰胺）（118）（PID 118）壳和锚定的抗Her 2 Fab部分分别有助于被动和主动靶向。这种FCIM的阿霉素（DOX）负载容量成功地增加了约2倍，通过物理增强的内部水库的疏水性，而没有结构变形。温度调控被动靶向和抗体导航主动靶向的细胞摄取和细胞内蓄积量是Doxil的4倍。对Her 2过表达胃癌细胞（N87 s）的细胞毒性试验显示，在T > VPTT时，在Fab的协同靶向下，FCIM的IC 50比Doxil的IC 50低约9倍。FCIM通过增加冠PID 118链密度（S-corona/N-agg）显示出高血清稳定性。在荷胃癌Balb/c裸鼠中评价体内组织分布。如通过IVIS（R）成像系统所观察到的，这种精细定制的FCIMs系统的肿瘤内积累在静脉内施用后24小时明显促进。由于其高稳定性和超靶向性，体内移植瘤的生长受到明显抑制，肿瘤相对体积增大
Micelles with high in vivo serum stability and intratumor accumulation post intravenous (i.v.) injection are highly desired for promoting chemotherapy. Herein, we finely synthesized and tailored well-defined anti-Her2 antibody Fab fragment conjugated immunomicelles (FCIMs), which showed interesting dual targeting function. The thermosensitive poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide)(118) (PID118) shell with volume phase transition temperature (VPTT: 39 degrees C) and the anchored anti-Her2 Fab moiety contributed to the passive and active targeting, respectively. The doxorubicin (DOX) loading capacity of such FCIMs was successfully increased about 2 times by physically enhanced hydrophobicity of inner reservoir without structural deformation. The cellular uptake and intracellular accumulation of DOX by temperature regulated passive and antibody navigated active targeting was 4 times of Doxil. The cytotoxicity assay against Her2 overexpression gastric cancer cells (N87s) showed that the IC50 of the FCIMs was similar to 9 times lower than that of Doxil under cooperatively targeting by Fab at T > VPTT. FCIMs showed high serum stability by increasing the corona PID118 chain density (S-corona/N-agg). In vivo tissue distribution was evaluated in Balb/c nude mice bearing gastric cancer. As observed by the IVIS (R) imaging system, the intratumor accumulation of such finely tailored FCIMs system was obviously promoted 24 h post i.v. administration. Due to the high stability and super-targeting, the in vivo xenografted gastric tumor growth was significantly inhibited with relative tumor volume