上转换介孔二氧化硅多功能肝癌诊疗纳米复合体系的构建
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摘要
本研究旨在设计一种用于肝癌诊疗用光激发载药上转换介孔二氧化硅纳米复合体系。首先应用油相法制备掺杂镱(Yb~(3+))、铒(Er~(3+))的上转换纳米颗粒(UCNP),并在颗粒表面包裹介孔二氧化硅(mSiO_2),其次在UCNP@mSiO_2中负载肝癌分子靶向治疗药物索拉菲尼(S)和光热荧光染料吲哚箐绿(ICG)。本研究利用可见光紫外光光谱,热成像等方法对纳米颗粒进行表征,并检测其载药性能和光热性能等。通过人肝癌细胞(HepG2)检测该纳米颗粒安全性、内吞效果及杀伤效果。实验结果表明该纳米颗粒具有较好的生物安全性,可在细胞内实现上转换荧光成像,并可有效杀伤肝癌细胞。本研究为该纳米颗粒在肝癌中的诊疗作用提供了有力支持。
To design a photoactivated drug-loaded upconversion mesoporous silica nanocomposite for the treatment of liver cancer. Firstly, the ytterbium(Yb~(3+)), erbium(Er~(3+)) doped upconversion nanoparticles(UCNP) were developed by oil phase method and covered with mesoporous silica(mSiO_2) on the surface. Secondly, molecular targeted drug sorafenib(S) and photothermal fluorescent dye indocyanine green(ICG) were loaded in UCNP@mSiO_2. In this study, visible light ultraviolet spectroscopy, thermal imaging and other methods were used to characterize drug-loading and photothermal properties of nanoparticles.Safety, endocytosis and cytotoxity effect of this nanoparticles were detected by human hepatoma cells(HepG2). These results indicate that this composite nanocarrier has good biosafety, can effectively kill tumor cells, and achieve up-conversion fluorescence imaging in tumor cells. Our study provides strong support for the diagnosis and treatment of liver cancer.
To design a photoactivated drug-loaded upconversion mesoporous silica nanocomposite for the treatment of liver cancer. Firstly, the ytterbium(Yb~(3+)), erbium(Er~(3+)) doped upconversion nanoparticles(UCNP) were developed by oil phase method and covered with mesoporous silica(mSiO_2) on the surface. Secondly, molecular targeted drug sorafenib(S) and photothermal fluorescent dye indocyanine green(ICG) were loaded in UCNP@mSiO_2. In this study, visible light ultraviolet spectroscopy, thermal imaging and other methods were used to characterize drug-loading and photothermal properties of nanoparticles.Safety, endocytosis and cytotoxity effect of this nanoparticles were detected by human hepatoma cells(HepG2). These results indicate that this composite nanocarrier has good biosafety, can effectively kill tumor cells, and achieve up-conversion fluorescence imaging in tumor cells. Our study provides strong support for the diagnosis and treatment of liver cancer.
引文
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[4]Khaliq N U,Sandra F C,Park D Y,et al.Doxorubicin/heparin composite nanoparticles for caspase-activated prodrug chemotherapy[J].Biomaterials,2016,101:131-142.
[5]Utsunomiya T,Shimada M,Kudo M,et al.A comparison of the surgical outcomes among patients with HBV-positive,HCV-positive,and non-B non-C hepatocellular carcinoma:a nationwide study of 11,950 patients[J].Annals of Surgery,2015,261(3):513-520.
[6]Sun M,Xu L,Ma W,et al.Hierarchical plasmonic nanorods and upconversion core-satellite nanoassemblies for multimodal imaging-guided combination phototherapy[J].Advanced Materials,2016,28(5):898-904.
[7]Jung H S,Han J,Lee J H,et al.Enhanced NIR radiation-triggered hyperthermia by mitochondrial targeting[J].Journal of the American Chemical Society,2015,137 (8):3017-3023.
[8]Hong G,Diao S,Antaris A L,et al.Carbon nanomaterials for biological imaging and nanomedicinal therapy[J].Chemical Reviews,2015,115(19):10816-10906.
[9]Zhang Z,Wang J,Nie X,et al.Near infrared laser-induced targeted cancer therapy using thermoresponsive polymer encapsulated gold nanorods[J].Journal of the American Chemical Society,2014,136(20):7317-7326.
[10]Qiu L,Chen T,Ocsoy I,et al.A cell-targeted,size-photocontrollable,nuclear-uptake nanodrug delivery system for drug-resistant cancer therapy[J].Nano Letters,2015,15(1):457-463.
[11]Kuo W S,Chang Y T,Cho K C,et al.Gold nanomaterials conjugated with indocyanine green for dual-modality photodynamic and photothermal therapy[J].Biomaterials,2012,33(11):3270-3278.
[12]Abels C.Targeting of the vascular system of solid tumours by photodynamic therapy (PDT)[J].Photochemical & Photobiological Sciences,2004,3(8):765-771.
[13]Zheng B,Chen HB,Zhao P Q,et al.Persistent luminescent nanocarrier as an accurate tracker in vivo for near infrared-remote selectively triggered photothermal therapy[J].ACS Applied Materials & Interfaces,2016,8(33):21603-21611.
[14]Lopez V,Villegas M R,Rodriguez V,et al.Janus mesoporous silica nanoparticles for dual targeting of tumor cells and mitochondria[J].ACS Applied Materials & Interfaces,2017,9(32):26697-26706.
[15]Jin R,Liu Z,Bai Y,et al.Multiple-responsive mesoporous silica nanoparticles for highly accurate drugs delivery to tumor cells[J].ACS Omega,2018,3(4):4306-4315.
[16]Su,Q,Feng W,Yang D,et al.Resonance energy transfer in upconversion nanoplatforms for selective biodetection[J].Accounts of Chemical Rsearch,2017,50(1):32-40.
[17]Gnanasammandhan M K,Idris N M,Bansal A,et al.Near-IR photoactivation using mesoporous silica-coated NaYF4:Yb,Er/Tm upconversion nanoparticles[J].Nature Protocols,2016,11(4):688-713.
[18]Zhang Y,Zhang L,Deng R,et al.Multicolor barcoding in a single upconversion crystal[J].Journal of the American Chemical Society,2014,136(13):4893-4896.