碳点复合聚多巴胺载药体系用于肿瘤协同治疗的评价

Carbon dots⁃polydopamine nanocomposite for synergistic tumor therapy

目的为了提高药物的治疗效果,降低毒性和不良反应,研究制备了一种基于碳点(CDs)修饰的聚多巴胺(polydopamine,PDA)的特异性药物递送系统。方法采用水热法制备直径约为4 nm的CDs,然后制备碳点复合聚多巴胺(PDA@CDs)载体。以盐酸阿霉素(DOX)作为模型药物,制备DOX/PDA@CDs载药体系。采用透射电子显微镜、Zeta电位、动态光散射和荧光光谱等对载药体系进行表征。模拟肿瘤微环境以及NIR光照射对载药体系进行体外释放的考察,采用细胞水平实验评价该体系的热疗和化疗协同治疗效果。结果PDA@CDs载体具有优良的光热性能和光热稳定性。体外释放曲线表明,在pH 7.4 PBS和无近红外光照射的情况下,DOX释放量较少,在高过氧化氢浓度、pH 5.0 PBS和近红外光照射下,DOX的释放显著增加。细胞摄取实验证明PDA@CDs能被细胞摄取,且可以发射绿色荧光。细胞毒实验表明,DOX/PDA@CDs在NIR光照后显示出优异的化疗/热疗协同杀伤肿瘤细胞的作用。结论DOX/PDA@CDs具有pH/H2O2/NIR多重响应性释药的特点,能够实现热疗与化疗的协同治疗效果,在癌症治疗领域具有光明的前景。

Objective To improve drug efficacy and reduce toxicity,a specific drug delivery system based on carbon dots(CDs)modified polydopamine(PDA)was constructed.Methods CDs with a diameter of ap⁃proximately 4 nm were prepared by hydrothermal method.Then,CDs were modified on the surface of PDA to prepare PDA@CDs carriers.Afterwards,doxorubicin hydrochloride(DOX)was used as the model drug to prepare DOX/PDA@CDs.Transmission electron microscopy(TEM),Zeta potential,dynamic light scat⁃tering(DLS)and fluorescence spectroscopy were used to characterize the drug loading system.In vitro re⁃lease behaviors of the drug loading system were investigated by simulating the tumor microenvironment and applying NIR light irradiation.Cell level experiments were conducted to investigate the synergistic effect of thermotherapy and chemotherapy.Results PDA@CDs had excellent photothermal property and photothermal stability.The in vitro release profile showed that without NIR light irradiation and pH 7.4 PBS,the release a⁃mount of DOX was low.However,under high concentration of H2O2,pH 5.0 PBS,and NIR light irradia⁃tion,the release of DOX increased significantly.Cellular uptake experiments proved that PDA@CDs could be uptaken by cells and emit green fluorescence.Cytotoxicity tests demonstrated that DOX/PDA@CDs showed brilliant chemo/photothermal synergistic effect on killing tumor cells after NIR irradiation.Conclu⁃sion DOX/PDA@CDs has pH/H2O2/NIR multi⁃responsive drug release characteristics,which can realize chemo/photothermal synergistic effect,thus owning a bright prospect in the field of cancer treatment.