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卵泡刺激素多肽修饰的纳米粒制备及体外靶向性研究

Preparation and in vitro targeting of follicle stimulating hormone polypeptide modified nanoparticles
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摘要 目的制备卵泡刺激素多肽修饰的纳米粒,并探讨其体外靶向性。方法用免疫细胞化学法检测人肝癌细胞BEL-7402、人卵巢上皮性癌细胞SKOV-3和Caov-3中卵泡刺激素受体的表达。合成卵泡刺激素B链第81~95个氨基酸片段,并与纳米粒共价连接。通过细胞形态学和流式细胞技术进行多肽和纳米粒的靶向性检测。结果制备的纳米粒直径为100nm左右,Zeta电位大约为-25mV。BEL-7402和SKOV-3细胞不表达卵泡刺激素受体,而Caov-3细胞的卵泡刺激素受体呈阳性表达。Caov-3细胞对卵泡刺激素多肽修饰的纳米粒的摄取能力为4.17±0.86,显著强于SKOV-3细胞的2.30±0.21,两者比较,差异有统计学意义(P〈0.05)。卵泡刺激素多肽修饰后,转运纳米粒的能力也显著增加,Caov-3细胞摄取卵泡刺激素多肽修饰纳米粒为4.17±0.86,而摄取纳米粒为0.41±0.32,两者比较,差异也有统计学意义(P〈0.05),且随着时间延长和浓度增加而增强。结论卵泡刺激素多肽修饰的纳米粒对卵泡刺激素受体阳性的卵巢上皮性癌细胞具有良好的靶向性,可能的机制为受体介导的特异性内吞作用。 Objective To prepare follicle stimulating hormone (FSH) polypeptide modified nanoparticles (NP) in order to achieve specific ovarian tumor targeting. Methods Expression of FSH receptor protein in human liver cancer and ovarian cancer cell lines BEL-7402, SKOV-3 and Caov-3 was detected by immunocytochemistry. The polypeptide fragment of FSH β 81 -95 amino acids (FSHL81-95) was synthesized and covalently coupled to NP. The specific binding of FSHL81-95 and FSHL81-95-NP was examined by fluorescence microscopy and flow cytometry. Results BEL-7402 and SKOV-3 cells were negative for FSH receptor staining, while Caov-3 cells were positive. The diameters of NP were about 100 nm, with a Zeta potential of - 25 mV or so. Caov-3 cells showed a more specific interaction with FSHL81-95-NP than SKOV-3 cells (4. 17 ±0. 86 and 2. 30 ±0. 21 ; P〈0. 05). The uptake of FSHL81-95- NP was more than NP in Caov-3 cells (4. 17 ±0. 86 and 0.41 ±0. 32; P 〈0. 05). FSHL81-95-NP showed a selective targeting at Caov-3 ceils compared with control NP. Conclusion FSH polypeptide modified NP could selectively target ovarian cancer cells expressing FSH receptor, which might contribute to specific endocytosis mediated by FSH receptor.
出处 《中华妇产科杂志》 CAS CSCD 北大核心 2008年第7期533-537,共5页 Chinese Journal of Obstetrics and Gynecology
基金 国家高技术研究发展计划(2006AA02Z342) 上海市重点学科建设计划(B117) 上海市科学技术委员会科研计划项目(044119601)
关键词 卵巢肿瘤 卵泡刺激素 Β亚单位 受体 FSH 纳米结构 药物释放系统 Ovarian nesplasms Follicle stimulating hormone, beta subunit Receptors, FSH Nanostructures Drug delivery systems
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