线性麦芽糊精聚合物功能化Fe_3O_4纳米复合物药物载体的合成和应用
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摘要
采用共沉淀法制备得到了线性麦芽糊精聚合物功能化的Fe_3O_4磁性纳米粒子(LM-SP-MNPs),通过傅里叶变换红外光谱、透射电子显微镜、热重分析等技术对其结构、形貌进行了表征。其粒径大小为(12±2) nm。选取抗癌药物盐酸阿霉素(DOX)作为模型药物,运用荧光光谱法研究了LM-SP-MNPs的载药性能和释放行为,探讨了p H值对LM-SP-MNPs药物释放性能的影响。最适p H条件下,LM-SP-MNPs对盐酸阿霉素的最大吸附量约为357. 1 mg/g,吸附等温线符合Freundlich等温吸附模型。LM-SP-MNPs与盐酸阿霉素的复合物(DOX@LM-SP-MNPs),在37℃的条件下药物在酸性条件下的释放效率大于中性条件。p H=5. 3时,盐酸阿霉素在7 h内的累积释放率为26. 9%。此外,细胞毒性试验表明,LM-SP-MNPs具有良好的生物相容性,而DOX@LM-SP-MNPs和肝癌细胞共培养后可以明显杀死Hep G2肝癌细胞。
Linear maltodextrin polymer modified magnetic nanoparticles( LM-SP-MNPs) were prepared by chemical co-precipitation. The structure and morphology of LM-SP-MNPs were characterized by Fourier transform infrared spectroscopy,transmission electron microscopy and thermogravimetric analysis. The loading and release behaviors of LM-SP-MNPs as drug carrier were evaluated by fluorescence spectroscopy using doxorubicin( DOX) as a model drug. The pH effects on LM-SP-MNPs for drug releasing were investigated.Under the optimal pH conditions,the maximum loading of DOX into LM-SP-MNPs is 357. 1 mg/g,and the loading behavior follows Freundlich adsorption balance equations with multilayer adsorption. Furthermore,the release ability of DOX@ LM-SP-MNPs is more efficient under acid solution than that under natural solution at37 ℃ in vitro. Accumulated release efficiency of DOX in 7 h is 26. 9% at p H = 5. 3. In addition,the MTT assays show that LM-SP-MNPs have an excellent biocompatibility,and the DOX@ LM-SP-MNPs decrease the relative cellular viability of HepG2 cells evidently.
Linear maltodextrin polymer modified magnetic nanoparticles( LM-SP-MNPs) were prepared by chemical co-precipitation. The structure and morphology of LM-SP-MNPs were characterized by Fourier transform infrared spectroscopy,transmission electron microscopy and thermogravimetric analysis. The loading and release behaviors of LM-SP-MNPs as drug carrier were evaluated by fluorescence spectroscopy using doxorubicin( DOX) as a model drug. The pH effects on LM-SP-MNPs for drug releasing were investigated.Under the optimal pH conditions,the maximum loading of DOX into LM-SP-MNPs is 357. 1 mg/g,and the loading behavior follows Freundlich adsorption balance equations with multilayer adsorption. Furthermore,the release ability of DOX@ LM-SP-MNPs is more efficient under acid solution than that under natural solution at37 ℃ in vitro. Accumulated release efficiency of DOX in 7 h is 26. 9% at p H = 5. 3. In addition,the MTT assays show that LM-SP-MNPs have an excellent biocompatibility,and the DOX@ LM-SP-MNPs decrease the relative cellular viability of HepG2 cells evidently.
引文
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[4]Jin C Z,Wang Y J,Tang H L,et al.Synthesis,Characterization and Catalytic Applications of Core-Shell Magnetic Carbonaceous Nanocomposites[J].J Phys Chem,2014,118(23):25110-25117.
[5]Ding Y,Yin H,Sun K N,et al.Chitosan-based Magnetic/fluorescent Nanocomposites for Cell Labelling and Controlled Drug Release[J].New J Chem,2017,41(4):1736-1743.
[6]Chowdhuri A R,Singh T,Ghosh S K,et al.Carbon Dots Embedded Magnetic Nanoparticles@Chitosan@Metal Organic Framework as a Nanoprobe for p H Sensitive Targeted Anticancer Drug Delivery[J].Appl Mater Interfaces,2016,8(26):16573-16583.
[7]Muniyandy S,Kesavan B,Gomathinayagam M,et al.Ultrasonically Controlled Release and Targeted Delivery of Diclofenac Sodium via Gelatin Magnetic Microspheres[J].Int J Pharm,2004,283(1/2):71-82.
[8]Issadore D,Park Y I,Shao H,et al.Magnetic Sensing Technology for Molecular Analyses[J].Lab Chip,2014,14(14):2385-2397.
[9]Pallab P,Jyotsnendu G,Finn R,et al.Targeted Temperature Sensitive Magnetic Liposomes for Thermo-chemotherapy[J].JControlled Release,2010,142(1):108-121.
[10]Lee S,Zhu X,Wang Y J,et al.Ultrasound,p H,and Magnetically Responsive Crown-Ether-Coated Core/Shell Nanoparticles as Drug Encapsulation and Release Systems[J].Appl Mater Interfaces,2013,5(5):1566-1574.
[11]Wang H,Wang K,Tian B,et al.Preloading of Hydrophobic Anticancer Drug into Multifunctional Nanocarrier for Multimodal Imaging,NIR-Responsive Drug Release,and Synergistic Therapy[J].Small,2016,12(46):6388-6397.
[12]Gou M,Li S,Zhang L,et al.Facile One-Pot Synthesis of Carbon/Calcium Phosphate/Fe3O4Composite Nanoparticles for Simultaneous Imaging and p H/NIR-Responsive Drug Delivery[J].Chem Commun,2016,52(74):11068-11071.
[13]KSwain A,Pradhan L,Bahadur D,et al.Polymer Stabilized Fe3O4Graphene as an Amphiphilic Drug Carrier for ThermoChemotherapy of Cancer[J].Appl Mater Interfaces,2015,7(15):8013-8022.
[14]Zhao W,Cui B,Peng H X,et al.Novel Method to Investigate the Interaction Force Between Etoposide and APTES-Functionalized Fe3O4@n Si O2@m Si O2Nanocarrier for Drug Loading and Release Processes[J].Phys Chem C,2015,119(8):4379-4386.
[15]Moorthy M S,Oh Y,Bharathiraja S,et al.Synthesis of Amine-polyglycidol Functionalised Fe3O4@Si O2Nanocomposites for Magnetic Hyperthermia,p H-responsive Drug Delivery,and Bioimaging Applications[J].RSC Adv,2016,6(113):110444-110453.
[16]Liang W T,Yang C,Zhou D Y,et al.Phase-controlled Supramolecular Photochirogenesis in Cyclodextrin Nanosponges[J].Chem Commun,2013,49(34):3510-3512.
[17]Wei X Q,Liang W T,Wu W H,et al.Solvent-and Phase-Controlled Photochirogenesis.Enantiodifferentiating Photoisomerization of(Z)-Cyclooctene Sensitized by Cyclic Nigerosylnigerose-Based Nanosponges Crosslinked by Pyromellitate[J].Org Biomol Chem,2015,13(10):2905-2912.
[18]GONG Tao,ZHAO Meiling,LIANG Wenting,et al.Adsorption of Malachite Green by Linear Maltodextrin Supramolecular Polymer[J].J Shanxi Univ(Nat Sci Ed),2017,40(2):316-323(in Chinese).弓韬,赵美玲,梁文婷,等.线性麦芽糊精超分子聚合物对孔雀石绿吸附性能研究[J].山西大学学报(自然科学版),2017,40(2):316-323.
[19]Gong T,Zhou Y H,Sun L L,et al.Effective Adsorption of Phenolic Pollutants from Water Usingβ-Cyclodextrin Polymer Functionalized Fe3O4Magnetic Nanoparticles[J].RSC Adv,2016,6(84):80955-80963.
[20]Yu S,Wu G,Gu X,et al.Magnetic and p H-sensitive Nanoparticles for Antitumor Drug Delivery[J].Colloids Surf B,2013,103(1):15-22.
[21]Sahoo B,Devi K S,Banerjee R,et al.Thermal and p H Responsive Polymer-Tethered Multifunctional Magnetic Nanoparticles for Targeted Delivery of Anticancer Drug[J].Appl Mater Interfaces,2013,5(9):3884-3893.