【摘要】 背景:近年来载抗癌药物磁性纳米微粒作为一种新型靶向给药系统,利用其高载药量、靶向定位输送、以及磁粒的热效应、可生物降解等优点,为高效、低毒副作用的化疗带来了新的希望。目的:观察顺铂耦合海藻酸钠改性磁性纳米球载体后对人鼻咽癌CNE2细胞的体外毒性效应。设计、时间及地点:体外对比观察实验,于2005-03 在中山大学北校区药理实验室完成。材料:顺氯氨铂(CDDP)由山东齐鲁制药厂提供,海藻酸钠改性载顺铂四氧化三铁磁性纳米球(CDDP-SAMNP),粒径大小43～52 nm,可逆释放的 CDDP 量(或利用率)约 65%。鼻咽癌CNE2细胞株由中山大学肿瘤医院细胞病理实验室提供。方法:实验分药物处理组及对照组,药物处理组分为 CDDP 组和 CDDP-SAMNP 组,CDDP 和 CDDP-SAMNP 均用 RPMI-1640培养液稀释,加药浓度按 CDDP 的含量计。对照组分别为 RPMI-1640 培养液组和单纯SAMNP 组(加入四氧化三铁,磁核质量浓度为 7 g/L,以培养液稀释)。主要观察指标:采用 MTT 法分别观察1.89～11.34 mg/L 的 CDDP 及相应剂量的CDDP-SAMNP对鼻咽癌CNE2细胞作用24, 48 h 后的杀伤率;并通过透射电镜观察CNE2 对 CDDP-SAMNP 的摄取。结果:①单纯 SAMNP 对鼻咽癌 CNE2 细胞无杀伤作用,与培养液组相似(P > 0.05)。②随着 CDDP 和 CDDP-SAMNP 药物浓度的增加,药物对 CNE2 细胞的杀伤率呈明显的量效关系。同一药物相同浓度下,随着作用时间的延长,杀伤率提高,呈明显的时效关系。作用 24 h,CDDP-SAMNP 对鼻咽癌CNE2 的杀伤率与 CDDP 相似(P > 0.05)。作用 48 h,中低浓度(1.89～5.04 mg/L)时,CDDP-SAMNP 的杀伤率低于 CDDP(P < 0.05),当达到 6.93 mg/L 时,杀伤率接近同浓度的 CDDP。③ CNE2细胞能够摄取CDDP-SAMNP 和 SAMNP。结论:在高浓度下阴离子海藻酸钠改性载顺铂磁性纳米球对鼻咽癌CNE2细胞的体外毒性与同浓度单纯顺铂相近,杀伤作用来源于载体释放的顺铂。改性后顺铂的稳定性提高,药效没有降低。更多还原

【Abstract】 BACKGROUND:Anticancer drugs-loaded magnetic nanoparticles,as a novel targeting drug delivery system,are characterized by high drug loading dose,targeting location transport,heat effect of magnetic grains,and biological degradation. Thus,this system brings new hopes for chemical therapy with high efficiency and low toxic and side effects. OBJECTIVE:To observe in vitro toxic effects of complexing cis-diaminedichloroplatinum (CDDP)-loaded magnetic nanoparticles on human nasopharyngeal carcinoma (NPC) CNE2 cells. DESIGN,TIME AND SETTING:The in vitro controlled study was performed at the Laboratory of Pharmacology,Northern Region,Sun Yat-sen University in March 2005. MATERIALS:CDDP was provided by Shandong Qilu Pharmaceutical factory. CDDP-loaded magnetic nanoparticles (CDDP-SAMNP),43-52 nm in particle diameter. Utilization rate of CDDP was about 65%. NPC CNE2 cell line was supplied by the Laboratory of Cell Pathology,Cancer Hospital,Sun Yat-sen University. METHODS:This study contained medication and control groups. The medication group was assigned to CDDP and CDDP-SAMNP groups. CDDP and CDDP-SAMNP were diluted by RPMI-1640 medium. Drug concentration was in accordance with CDDP content. The control group was divided into RPMI-1640 medium and SAMNP groups (adding ferroso-ferric oxide,magnetic nucleus concentration was 7 g/L,diluted by the medium). MAIN OUTCOME MEASURES:MTT assay was used to observe kill and wound rate of 1.89-11.34 mg/L CDDP and corresponding dose of CDDP-SAMNP on NPC CNE2 cells following 24 and 48 hours. Uptake of CDDP-SAMNP by CNE2 cells was investigated under a transmission electron microscope. RESULTS:SAMNP as the medium group had no effect on killing or wounding CNE2 cells (P > 0.05). With the increment of CDDP and CDDP-SAMNP dose,the kill and wound rate presented an obvious dose-effect relationship. At the same dose,the same medicine showed an increasing kill and wound rate with the extension of reaction time,presenting an obvious time-effect relationship. At 24 hours after reaction,the kill and wound rate of CDDP-SAMNP and CDDP were similar (P > 0.05). At 48 hours,at the dose from 1.89 to 5.04 mg/L,the kill and wound rate of CDDP-SAMNP was lower than that of CDDP (P < 0.05),but when increased to 6.93 mg/L,the kill and wound rate of CDDP-SAMNP was close to that of CDDP. SAMNP and CDDP-SAMNP could be easily taken into CNE2 cells. CONCLUSION:Effect of CDDP-SAMNP on killing and wounding NPC CNE2 cells is close to that of cis-diaminedichloroplatinum at the same high dose. The active sources are the cis-diaminedichloroplatinum released from the nano-carriers. The stability of modified CDDP-SAMNP has been increased and its therapy effect has not been influenced.更多还原