透明质酸修饰的介孔二氧化硅包覆金纳米棒的制备及在肿瘤化疗-热疗联合治疗中的应用

doi:10.7503/cjcu20150662

摘要/Abstract

摘要：

通过在包覆了金纳米棒的介孔硅表面修饰生物相容性的透明质酸, 得到了具有肿瘤靶向性的多功能药物载体. 实验结果表明, 透明质酸可以通过酰胺键修饰在介孔硅表面, 所得药物载体可在透明质酸酶作用下实现选择性释放. 该体系在近红外区域具有较高的吸收, 可以在近红外光照射下实现光热转换. 细胞实验结果表明, 该多功能药物载体可以有效靶向CD44过量表达的乳腺癌细胞, 通过CD44介导的内吞富集在肿瘤内部, 结合化学药物治疗和光热治疗, 显示出更高的肿瘤细胞凋亡效率.

关键词: 介孔二氧化硅, 金纳米棒, 透明质酸, 化疗-热疗联合治疗

Abstract:

A tumor-targeting multifunctional drug delivery system was obtained through modifying mesoporous silica-coated gold nanorods with biocompatible hyaluronic acid. The experimental results demonstrated hyaluronic acid could be modified on the surface of mesoporous silica through the formation of amide bond. The resulted drug carrier could realize enzyme-responsive drug release in the presence of hyaluronidase. UV-Vis spectra showed that the system had a high absorption in the near infrared region, thus exhibiting photothermal effect upon the near infrared light irradiation. Besides, cell experiments demonstrated the multifunctional drug carrier could effectively target CD44 over-expressed breast cancer cells. It could be accumulated in the tumor region through CD44 receptor mediated endocytosis. Combining chemo- and photothermal therapy resulted in improved tumor apoptosis efficiency.

Key words: Mesoporous silica, Gold nanorods, Hyaluronic acid, Chemo-photothermal therapy

中图分类号:

TrendMD:

金新天, 刘刚, 李君哲, 孙丽丽, 王俊荣, 李俊锋, 李沛, 陈文庆, 王强, 佟倜. 透明质酸修饰的介孔二氧化硅包覆金纳米棒的制备及在肿瘤化疗-热疗联合治疗中的应用. 高等学校化学学报, 2016, 37(2): 224.

JIN Xintian, LIU Gang, LI Junzhe, SUN Lili, WANG Junrong, LI Junfeng, LI Pei, CHEN Wenqing, WANG Qiang, TONG Ti. Preparation of Hyaluronic Acid-modified Mesoporous Silica-coated Gold Nanorods and Their Application in Chemo-Photothermal Therapy of Cancer. Chem. J. Chinese Universities, 2016, 37(2): 224.

图/表 14

Scheme 1 Synthetic routes of the multifunctional drug delivery system(hyaluronic acid-modified mesoporous silica-coated gold nanorods) and the mechanism of chemo- and photothermal therapy

Fig.1 Schematic illustration of CD44 receptor-mediated endocytosis of nanoparticles and subsequent chemotherapy and NIR-induced hyperthermia

Fig.2 TEM images of AuNR@SiO2(A) and AuNR@SiO2-HA(B, C)

Fig.3 Absorption spectra(A) of AuNR@SiO2(a), AuNR@SiO2-HA(b) and Dox-AuNR@SiO2-HA(c) and FTIR spectra(B) of AuNR@SiO2-NH2(a) and AuNR@SiO2-HA(b)

Fig.4 Zeta potential of AuNR@SiO2(a), AuNR@SiO2-NH2(b) and AuNR@SiO2-HA(c)

Fig.5 Hydrodynamic diameters of AuNR@SiO2 and AuNR@SiO2-HA

Fig.6 Photothermal curves of H2O and AuNR@SiO2-HA under NIR laser irradiation as a function of time

Fig.7 Thermographs of H2O(a) and AuNR@SiO2-HA(808 nm, 1.8 W/cm2, 8 min)(b) mea-sured by infrared thermal imaging camera

Fig.8 Drug release profiles from Dox-AuNR@SiO2-HA at different conditions

Fig.9 Confocal laser scanning microscopy investigation of the localization of AuNR@FITC-SiO2-HA to MDA-MB-231 cells (A) Blue fluorescence from nuclear stain DAPI; (B) green fluorescence from AuNR@FITC-SiO2-HA;(C) bright-field image; (D) combined image of (A) to (C).

Fig.10 Flow cytometry analysis of uptake efficiency of nanoparticles by MDA-MB-231(A) and NIH-3T3(B) cells Red: AuNR@FITC-SiO2; green: AuNR@FITC-SiO2-HA.

Fig.11 In vitro viability of MDA-MB-231 cells in the presence of AuNR@SiO2-HA and Dox-AuNR@SiO2-HA

Fig.12 In vitro viability of NIH-3T3 cells in the presence of AuNR@SiO2-HA and Dox-AuNR@SiO2-HA

Fig.13 In vitro viability of MDA-MB-231 cells in the presence of Dox-AuNR@SiO2-HA with or without laser irradiation

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