中文摘要
目前对晚期肝细胞癌患者缺乏有效的治疗手段,纳米生物技术在肿瘤的诊断治疗研究中显示出良好的应用前景。本课题拟构建一种多功能的磁性量子点纳米颗粒(C225-Fe3O4@SiO2@Qdots/PS),以其作为载体将肝癌特异性表达荧光素酶基因转染细胞后,量子点能被非结合的生物发光激发, 所以携带荧光素酶基因的磁性量子点可以作为一种肝癌特异性的自发光纳米颗粒,用这种自发光纳米颗粒作为能量的供体,在满足能量共振转移的条件下可以激发作为受体的光敏剂,从而对肝癌细胞进行靶向自发光光动力学治疗。同时磁性纳米颗粒具有磁响应性,可在交变磁场中对肝癌细胞进行磁流体热疗,改善肿瘤局部乏氧状态从而提高光动力学的疗效,二者联合治疗具有协同作用。纳米颗粒表面修饰的西妥昔单抗C225能竞争性结合肿瘤表面的EGFR,抑制肿瘤增殖转移、诱导细胞凋亡,并进一步增加治疗的靶向性。本系统为探索靶向性、多模式肿瘤治疗提供新思路。
英文摘要
The multi-functionalized magnetic quantum dots nanoparticles (C225-Fe3O4@SiO2@Qdots/PS) will be prepared and act as gene carriers to deliver the hepatoma-specific expressing luciferase into hepatocellular carcinoma cells. For quantum dots can be excited by unbound bioluminescence, the luciferase gene-loaded magnetic quantum dots thus act as hepatoma specific self-illuminating nanoparticles. Using the self-illuminating nanoparticles as donors and potosensitizers (PS) as the receptor in a FRET (fluorescence resonance energy transfer) system, the PS could be excited and photodynamic therapy (PDT) effects were generated. Meanwhile the magnetic quantum dos could magnetic-inducing heating and kill the cancer cells when exposed to an altering magnetic field (AMF), which could increase the oxygen in tumor microenvironment and achieve the synergistic effect when combined with PDT. The epidermal growth factor receptor mono clone anatibody-C225 on the surface of the nanoparticles will inhibit the proliferation and metastasis of tumor cells, and proved more targeting for tumoricidal effects. The multifunctional system has perspective in hepatocellular carcinoma targeted and multi-modes treatment.
