| 敬雨亭,熊 翔,明 阳,杨 光,赵静雅,周绍兵.具有pH响应及细胞核靶向功能的胶束的体内抗肿瘤活性的研究[J].,2018,(1):12-17 |
| 具有pH响应及细胞核靶向功能的胶束的体内抗肿瘤活性的研究 |
| Study on the in vivo Antitumor Efficacy of the pH Responsive and Nuclear Targeting Micelles |
| 投稿时间：2017-04-23 修订日期：2017-05-17 |
| DOI：10.13241/j.cnki.pmb.2018.01.003 |
| 中文关键词: 胶束 细胞核靶向 pH响应 原位乳腺癌 体内抗肿瘤 |
| 英文关键词: Micelle Nuclear targeting pH Responsive Orthotopic breast cancer In vivo antitumor |
| 基金项目:国家自然科学基金项目（51373138; 21574105; 51603172） |
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| 中文摘要: |
| 摘要 目的：研究具有pH响应性及细胞核靶向功能的，由细胞穿透肽Tat修饰的聚乙二醇-聚己内酯共聚物胶束(PECL/DA-Tat-M)的体内抗肿瘤活性。方法：用溶剂挥发法制备了胶束，通过透射电镜（TEM）观察胶束形貌和大小。考察在不同pH条件下胶束的药物释放行为。在Bal b/c雌性小鼠的乳腺脂肪垫注射鼠源4T1乳腺癌细胞，建立小鼠乳腺癌原位模型，通过尾静脉向荷瘤小鼠注射具有pH响应及细胞核靶向功能的载药胶束。记录18天治疗期内肿瘤的体积、小鼠体重以及存活率的变化情况，并进行肿瘤组织的免疫组化研究。结果：TEM结果显示PECL/DA-Tat-M胶束呈球形结构，粒径在80 nm左右。在72小时内，胶束在pH 5.0条件释放80 %的药物，而在pH 7.4条件下仅释放11 %的药物。PECL/DA-Tat-M胶束组小鼠的肿瘤生长最缓慢，在治疗第18天，非靶向胶束(PECL-M)组肿瘤体积为0.82 cm3，PECL/DA-Tat-M组的肿瘤体积仅有0.51 cm3。生理盐水(Saline)组和空白胶束(PECL/DA-Tat-blank M)组的小鼠的肿瘤生长较为迅速，体积分别是PECL/DA-Tat-M胶束组肿瘤体积的4.43倍和3.76倍，差异具有统计学意义(P<0.05 或P<0.01)；各组小鼠经过治疗后体重均呈现出上升趋势；治疗期后第42天，PECL/DA-Tat-M胶束组和非靶向胶束(PECL-M)组小鼠的存活率分别为60 %和40 %，其他组的小鼠均在39天内全部死亡(n=5)；肿瘤组织免疫组化分析结果表明PECL/DA-Tat-M载药胶束能有效抑制肿瘤生长，其抑瘤率(IR)、及肿瘤细胞凋亡率(AR)明显高于其他组，差异具有统计学意义(P<0.05)。结论：具有pH响应及细胞核靶向功能的胶束(PECL/DA-Tat-M)具有良好的体内抗乳腺癌活性。 |
| 英文摘要: |
| ABSTRACT Objective: To study the in vivo antitumor efficacy of the pH responsive and nuclear targeting micelles (PECL/DA-Tat-M), which was assembled by Tat and DA modified PEG-PCL copolymer. Methods: The micelle was prepared by using the solvent evaporation method. The morphology and the size were observed via transmission electron microscope (TEM). And the drug release behavior under different pH condition was detected through high performance liquid chromatography (HPLC). The orthotopic 4T1 mouse breast tumor model was established by injecting the 4T1 tumor cells on the right mammary gland of female Balb/c mice. The drug loaded micelles PECL/DA-Tat-M were injected into the mice via tail vein. The tumor volumes, body weight and the survival rate of the mice were recorded in the 18-day treatment period, and the immunohistochemically analysis of the tumor tissue was also performed. Results: The results of TEM analysis revealed the spherical morphology of the micelles, the size of which was about 80 nm. The micelle released 80 % of the drug at pH 5.0 in 72 h, while only 11 % of the drug was released at pH 7.4 in 72 h. The tumor of the PECL/DA-Tat-M group grew slowly. 18 days after the first treatment, the tumor volume of the non-targeting micelle (PECL-M) group was 0.82 cm3, while that of the PECL/DA-Tat-M group was only 0.51 cm3. The tumor of the saline group and the blank micelle (PECL/DA-Tat-blank M) group grew quickly, The tumor volume was 4.43 folds and 3.76 folds much larger than that of the PECL/DA-Tat M group, respectively, the difference was statistically significant (P<0.05 or P<0.01). The mice body weight of all the groups exhibited an increasing tendency. 42 days after the first treatment, the survival rates of the PECL/DA-Tat-M group and the non-targeting micelle group were 60 % and 40 %, respectively. The mice of other groups all died before the 39th day after the first treat- ment (n=5). The results of the tumor immunohistochemical analysis indicated the PECL/DA-Tat-M could inhibit the tumor effectively, both the tumor inhibition rate and apoptotic rate of which were much higher than that of other groups, the difference was statistically significant (P<0.05). Conclusion: The pH responsive and nuclear targeting micelle (PECL/DA-Tat-M) exhibits good in vivo antitumor effi- cacy. |
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