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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。
BACKGROUND: In recent years, magnetic nanoparticles containing anti-cancer drugs as a new targeted drug delivery system, the use of its high drug loading, targeted delivery, and the thermal effects of magnetic particles, biodegradable, etc., for efficient, low toxicity Side effects of chemotherapy have brought new hope. OBJECTIVE: To observe the in vitro cytotoxicity of cisplatin-conjugated sodium alginate-modified magnetic nanosphere on human nasopharyngeal carcinoma CNE2 cells. DESIGN, TIME AND SETTING: An in vitro comparative observation experiment was performed at the Pharmacological Laboratory of Sun Yat-sen University in 2005-03. MATERIALS: Cisplatin (CDDP) was supplied by Qilu Pharmaceutical Factory in Shandong Province. Sodium alginate modified CDDP-SAMNP with diameter of 43 ~ 52 nm and CDDP amount of reversible release (Or utilization) about 65%. CNE2 cell line of nasopharyngeal carcinoma was provided by the Cytopathology Laboratory of Cancer Hospital of Sun Yat-sen University. Methods: The experiment was divided into drug treatment group and control group. Drug treatment components were CDDP group and CDDP-SAMNP group. Both CDDP and CDDP-SAMNP were diluted with RPMI-1640 medium, and drug concentration was calculated according to CDDP content. The control group was RPMI-1640 culture medium group and SAMNP group (ferroferric oxide was added, the concentration of magnetic core was 7 g / L, diluted with culture medium). MAIN OUTCOME MEASURES: The killing rates of CNE2 cells in nasopharyngeal carcinoma cells CNE2 cells after treated with CDDP of 1.89 ~ 11.34 mg / L and corresponding dose of CDDP-SAMNP were respectively observed by MTT method. Transmission electron microscope was used to observe the effect of CNE2 on CDDP-SAMNP Ingestion. Results: ① SAMNP alone had no cytotoxic effect on CNE2 cells in nasopharyngeal carcinoma, which was similar to that in culture medium (P> 0.05). ② With the increase of CDDP and CDDP-SAMNP drug concentration, the drug-killing rate of CNE2 cells showed a significant dose-response relationship. The same concentration of the same drug, with the extension of the role of time, the killing rate increased, showing a significant aging relationship. The effect of CDDP-SAMNP on CNE2 nasopharyngeal carcinoma was similar to that of CDDP (P> 0.05). The killing rate of CDDP-SAMNP was lower than that of CDDP (P <0.05) at medium and low concentration (1.89-5.04 mg / L) for 48 h. When the concentration reached 6.93 mg / L, the killing rate of CDDP-SAMNP was close to the same concentration of CDDP. ③ CNE2 cells can uptake CDDP-SAMNP and SAMNP. CONCLUSION: The in vitro cytotoxicity of CNS-modified magnetic nanoparticles loaded with cisplatin on CNE2 cells was similar to that of cisplatin at the same concentration. The killing effect was derived from the release of cisplatin. Modified cisplatin stability improved, no reduction in efficacy.