姜黄素-多巴胺纳米药物用于脑胶质瘤细胞的化疗-光热联合治疗

Curcumin-dopamine nanomedicines for combined chemo-photothermal therapy of glioma cell

关键词:  姜黄素  脑胶质瘤  纳米药物控释  化疗-光热联合治疗

Key words:  curcumin  glioma  nanomedicine controlled release  combined chemo-photothermal therapy

摘要:

[目的]探索一种药物递送系统改善姜黄素水溶性差、体内代谢快等问题，实现姜黄素-光热联合治疗脑胶质瘤细胞的目的。[方法]利用盐酸多巴胺在弱碱性条件下能够自聚合为聚多巴胺的特性，制备包封姜黄素的聚多巴胺纳米粒（PDA@CUR NPs），对纳米粒的粒径、粒径稳定性、表面Zeta电位、载药量、包封率、药物释放和光热转换性能进行考察；细胞水平上，利用激光扫描共聚焦显微镜探讨PDA@CUR NPs跨越血脑屏障的体外模拟和脑胶质瘤细胞对PDA@CUR NPs的摄取行为；通过细胞增殖及毒性实验，评估了PDA@CUR NPs对脑胶质瘤细胞的“化疗+光热疗法”联合治疗效果。[结果]PDA@CUR NPs粒径大小约275 nm，分布均匀，稳定性良好，载药量（11.41±0.27）%，包封率（81.73±2.22）%，在近红外光的外源性刺激下，5 min内温度能够达到约45℃；实现对负载姜黄素的光热及pH响应控制释放；细胞实验结果表明：PDA@CUR NPs能够跨越带孔小室（孔径0.4 μm），脑胶质瘤细胞能够摄取纳米粒，且姜黄素与光热的联合对脑胶质瘤细胞有显著的抑制杀伤作用。[结论]PDA@CUR NPs能够明显改善姜黄素水溶性、稳定性差和体内代谢快等问题，为化疗协同光热或其他疗法的联合治疗脑胶质瘤提供了新的思路。

Abstract:

[Objective] To explore a drug delivery system to improve the poor water solubility of curcumin and rapid metabolism in vivo,and to achieve the purpose of curcumin-photothermal combination therapy for glioma cells.[Methods] Using the characteristics that dopamine hydrochloride can self-polymerize into polydopamine under weakly alkaline conditions,polydopamine nanoparticles (PDA@CUR NPs) entrapped curcumin were prepared to investigate the particle size,particle size stability,surface zeta potential,drug loading,entrapment efficiency,drug release and photothermal conversion properties of nanoparticles;at the cellular level,laser scanning confocal microscopy was used to investigate the in vitro simulation of PDA@CUR NPs crossing the blood-brain barrier and the uptake behavior of PDA@CUR NPs by glioma cells. Through cell proliferation and toxicity experiments,the combined therapeutic effect of PDA@CUR NPs on glioma cells was assessed.[Results] PDA@CUR NPs had a particle size of about 275 nm,uniform distribution and good stability,with a drug loading of (11.41±0.27)% and an entrapment efficiency of (81.73±2.22)% and the temperature could reach about 45℃ within 5 min under exogenous stimulation with near-infrared light. The photothermal and pH response of curcumin-loaded NPs was controlled and released. The results of cell experiments showed that PDA@CUR NPs could bypass the pored chamber(pore size 0.4 μm),glioma cells could uptake nanoparticles and the combination of curcumin and photothermal had a significant inhibitory killing effect on glioma cells.[Conclusion] PDA@CUR NPs can significantly improve the water solubility,poor stability and rapid metabolism of curcumin in vivo,providing a new idea for the combined treatment of glioma with chemotherapy combined with photothermal or other therapies.