摘　要：为了增强光敏剂光动力治疗白血病的效果，研究由肿瘤靶向性分子叶酸（FA）修饰、壳聚糖纳米粒子（CS-NP）包裹Fe-TiO2 形成的复合纳米颗粒FA-CS@Fe-TiO2 对HL60细胞的光催化灭活作用。通过溶胶-凝胶法、两步法以及表面修饰等方法制备了FA-CS@Fe-TiO2 纳米颗粒，并利用X射线衍射（XRD）、扫描电镜（SEM）、傅里叶红外光谱等分析手段对纳米颗粒进行了表征。使用CCK-8法、活性氧含量分析法对复合纳米颗粒FA-CS@Fe-TiO2光催化灭活HL60细胞的作用机理进行了分析。细胞试验结果表明，在非光照条件下，壳聚糖（CS）本身对细胞的生长无明显抑制作用，且在低质量浓度（5µg/mL）时对细胞生长有一定的促进作用。相比Fe-TiO2 和FA-CS@Fe-TiO2纳米材料，CS@Fe-TiO2的毒性要明显降低，即使在160µg/mL的高质量浓度作用下，CS@Fe-TiO2（3:2）作用后的HL60细胞相对存活率仍可高达85%，说明CS的包裹能提高Fe-TiO2的生物相容性。光动力疗法（PDT）试验表明，FA的修饰可以显著提高HL60细胞对复合纳米颗粒的摄取，增强复合纳米颗粒对HL60细胞的灭活效率，FA-CS@Fe-TiO2的最高PDT灭活效率为78.75%。该研究为光动力疗法治疗白血病肿瘤细胞的临床应用提供了参考。
关键词：FA-CS@Fe-TiO2；肿瘤分子靶向；生物相容性；光动力疗法；HL60细胞
中图分类号：R454.2　　　　　　文献标志码：A　　　　　　 DOI: 10.3969/j.issn.1007-7146.2020.06.006

Abstract: In order to enhance the effect of photosensitizer photodynamic therapy on leukemia, the photocatalytic inactivation effects of composite nanoparticles FA-CS@Fe-TiO2 on HL60 cells were studied. The composite nanoparticles FA-CS@Fe-TiO2 were formed by the modification of tumor-targeting molecule folic acid (FA), plus Fe-TiO2 was wrapped by chitosan nanoparticles (CS-NP). FA-CS@Fe-TiO2 nanoparticles were prepared by sol-gel method, two-step method, and surface modification method, and analyzed by X-ray diffraction (XRD), scanning electron microscopy (SEM), and Fourier infrared spectroscopy. The CCK-8 method and active oxygen content analysis method were used to analyze the mechanism of FA-CS@Fe-TiO2 photocatalytic inactivation of HL60 cells. Cell test results showed that under non-light conditions, chitosan (CS) itself had no obvious inhibitory effect on cell growth, and it had a certain promotion effect on cells at low mass concentrations of 5µg/mL. Compared to Fe-TiO2 and FA-CS@Fe-TiO2 nanomaterials, the toxicity of CS@Fe-TiO2 was significantly reduced, and even at a high quality concentration of 160µg/mL, the relative survival of HL60 with CS@Fe-TiO2 (3:2) can still be as high as 85%, which indicates that the coating of chitosan can improve the biocompatibility of the composite nanoparticles. Photodynamic therapy (PDT) tests have shown that folic acid modification can significantly increase the uptake of composite nanoparticles by HL60 cells and enhance its inactivation efficiency to HL60 cells. The highest PDT inactivation effect of FA-CS@Fe-TiO2 nanoparticles was 78.75%. It provides a reference for the clinical application of photodynamic therapy in the treatment of leukemia tumor cells.
Key words: FA-CS@Fe-TiO2; tumor molecular targeting; biocompatibility; photodynamic therapy; HL60 cells