目的:制备温度和pH双重响应的核壳结构磁性荧光介孔二氧化硅纳米粒子用于抗肿瘤药物传输以及协同光动力治疗。方法:采用溶剂热法、反相胶束法制备实心硅包覆的Fe3O4核,以改良的溶胶凝胶法制备介孔硅中间层,再以种子沉淀聚合法在介孔硅表面修饰温敏聚合物壳层,得到Fe3O4@SiO2(F)@mSiO2(P)@P(NIPAM—CO—AA)纳米粒子。利用透射电子显微镜(TEM)对其形貌进行了表征。以盐酸阿霉素为模型药考察了该纳米粒子对药物的负载与释放行为,并采用MTT比色法对其进行了体外细胞活性评价。结果:TEM表征结果显示,该纳米粒子平均粒径约为300nm。药物负载与释放结果表明,该纳米粒子不仅具有较高的载药量(206.75±17.59)μg/mg和包封率(68.91±5.86)wt%,药物释放也呈现明显的温度和pH依赖性。MTT结果表明,载药的纳米粒子在680nmLED灯照射条件下与单用化学治疗和光动力治疗相比,对细胞的毒性明显增大(P〈0.01)。结论:Fe3O4@SiO2(F1@mSiO2(P)@P(NIPAM—CO—AA)纳米粒子可作为一个抗肿瘤药物载体,实现肿瘤化疗和光动力治疗的协同研究。
Objective: To prepare temperature-pH responsive and core-shell-structured magnetic fluorescent mesoporous silica nanopartieles for antitumor drug delivery and photodynamic therapy. Methods: First, the core of nonporous silica coated Fe3O4 was prepared via solvothermal reaction and reverse micelle method, then mesoporous silica as the middle layer was further coated on the core by modified sol-gel process, and finally the Fe3O4@SiO2(F)@mSiO2(P)@P(NIPAM-co-AA) nanoparticles were prepared with the polymer shell modified on the middle layer through seed precipitation polymerization. Transmission electron microscopy (TEM) was carried out to characterize the morphology of the nanoparticles. Doxorubicin hydrochloride (DOX) was used as a model drug to investigate the drug loading and releasing behavior. And MTT assay was adopted to evaluate the bioeompatibility and cytotoxicity of the nanoparticles. Results: The results of TEM showed that the average diameter of the nanoparticles was 300 nm. The drug loading and releasing results indicated that the nanoparticles exhibited an excellent drug loading content of (206.75±17.59) μg/mg and encapsulation efficiency of (68.91±5.86)wt%,and controlled drug releasing could be obtained by changing the temperature or pH values. MTT assay showed that the cytotoxic effect of DOX- loaded nanoparticles irradiated with a 680 nm LED lamp was significantly higher than that achieved by chemotherapy and photodynamic therapy alone. Conclusion: Fe3O4@SiO2(F)@mSiO2(P)@P(NIPAM-co-AA) nanoparticles could be used as an antitumor drug carrier to achieve a synergistic effect by combining chemotherapy and photodynamic therapy.