肿瘤血管靶向隐形纳米粒对HCT-15和HUVEC的细胞毒性评价  

Cytotoxicity of Stealth Nanoparticles Targeting to Tumor Neovasculature to HCT-15 and HUVEC Cells

作　　者：白帆[1] 於得红[1] 王超[1] 管滢芸[1] 陆琴[1] 方超[1] 

机构地区：[1]上海交通大学医学院药理学教研室,上海200025

出　　处：《现代生物医学进展》2012年第18期3420-3424,3419,共6页Progress in Modern Biomedicine

基　　金：国家自然科学基金项目(30873179)

摘　　要：目的:优化制备K237多肽修饰的紫杉醇隐形纳米粒(K237-PTX-NP),并评价其对HCT-15和HUVEC两种细胞的细胞毒性。方法:乳化-溶剂挥发法优化制备K237-PTX-NP;HPLC法测定其包封率、载药量;激光粒度分析仪测定其粒径和Zeta电位;CBQCA试剂盒测定纳米粒表面多肽密度。以Taxol和PTX-NP为对照,采用CCK-8方法研究比较K237-PTX-NP对HCT-15和HUVEC细胞的细胞毒性差异。结果:优化制备的K237-PTX-NP粒径为约150 nm,Zeta电位为-20 mv,包封率为33.5%,载药量为2.8%,多肽连接效率为24.5%,平均每个纳米粒表面连接的K237数目约为474个。作用24 h时,K237-PTX-NP抑制HUVEC活性的IC50为0.01 nM,而抑制HCT-15活性的IC50大于1μM。结论:与HCT-15相比,HUVEC对K237-PTX-NP高度敏感,提示K237-PTX-NP具有潜在通过抑制肿瘤血管内皮细胞的生长治疗以HCT-15为代表的、P-gp等膜转运蛋白高表达的耐药肿瘤的能力。Objective： To optimize paclitaxel-loaded stealth nanoparticles decorated with K237 peptides （K237-PTX-NP） and evaluate the cytotoxicity to HCT-15 and HUVEC cells. Methods： Paclitaxel-loaded stealth nanoparticles decorated with K237 peptides （K237-PTX-NP） were prepared by emulsification-evaporation method. The encapsulation efficiency and drug loading were determined by HPLC. The particle sizes, polydispersity, zeta potential were measured by dynamic light scattering assay. K237 density on the nanoparticle surface was determined by CBQCA Protein Quantitation Kit. With Taxol and PTX-NP as control, the cytotoxicity of K237-PTX-NP to HCT-15 and HUVEC were determined using CCK-8 assay. Results： The average particle size of K237-PTX-NP was 150 nm. The zeta potential was -20 mV; Encapsulating efficiency was 33.5 %; Drug loading was 2.8 %, K237 conjuation efficiency was 24.5 % and K237 density on the nanoparticle surface was 474. After 24 h incubation, the IC50 values of K237-PTX-NP for HUVEC and HCT-15 cells were about 0.01 nM and over 1 ixM respectively. Conclusion＂ Compared with HCT-15 cells, HUVEC cells are much more sensitive to K237-PTX-NP, which suggested that K237-PTX-NP may have the capacity to treat multidrug resistant tumors like HCT-15, and it was highly expressed with P-gp or other multidrug resistance associated proteins, through inhibiting the growth of tumor endothelial cells.

关 键 词：隐形纳米粒 紫杉醇 多药耐药 HCT-15 

分 类 号：R730.5[医药卫生—肿瘤] R943[医药卫生—临床医学]