A novel redox-sensitive system based on single-walled carbon nanotubes for chemo-photothermal therap

来源 :第二届全国生物颗粒学术研讨会、第三届国际工业药学和临床药学研讨会暨第一届岭南国际药学大会 | 被引量 : 0次 | 上传用户:wangxunzhi520
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  Objective This study was to prepare and characterize a novel redox-sensitive system which was modified by SWCNTs-HA carrying both anticancer drug, doxorubicin (DOX) and MRI CAS;in addition, the in vitro cellular uptake study and In vivo MRI images were also studied.Method In our work, a novel redox-sensitive system constructed from hyaluronic acid,single-walled carbon nanotubes (SWCNTs), doxorubicin (DOX) and gadolinium (Gd) were successfully developed.Their morphology was investigated by transmission electron microscopy (TEM) and hyperspectral microscopy.The DOX release in vitro were conducted in PBS (pH 7.4, 0.01 M) with different GSH levels (0, 10 μM, 10 mM and 20 mM) and gently shaken at 37 ℃ in a water bath at 100 rpm.The in vitro cofocal laser scanning microscopy (CLSM) was employed to visualize the intracellular distribution.And the In vivo MRI images of the mice were acquired using a Litz coil on a 1.5 T clinical MRI scanner.Results The representative TEM image of SWCNTs and modified SWCNTs were shown in Fig.1A (a, b).Clearly, SWCNTs-COOH appeared to be smooth and without impurities after cutting and cleaning, when coated with HA, the polysaccharide chains could be observed on the sidewalls of SWCNTs.Moreover, as shown in Fig.1A (c), when DOX was conjugated with HA modified SWCNTs, uniformly coated nanotubes could be obtained.In addition,hyperspectral imaging analysis (Fig.1B) validate that the successful conjugation of HA and DOX with SWCNTs.The release behaviors of DOX from Gd/SWCNTs-HA-ss-DOX showed that about 57.7% of DOX was released in 4 h and almost 80.2% while the release of DOX from other groups was slow (Figure.2).The CLSM results displayed that redox-sensitive annotates could provide an effective approach for rapid transport of cargo into the cytosol,where the cargo could exert its function.(Fig3).As shown in Fig.4, the tumor interior of Gd/SWCNTs-HA-ss-DOX exhibited much stronger T1 contrast enhancements gradually during the time course than Gd/SWCNTs-COOH whereas there was an immediately enhancement in signal intensity for Gd-DTPA group at first 0.5 h, it decreased quickly to the normal level.Conclusion The results demonstrated that a multifunctional tumor targeting Gd/SWCNTs-HA-ss-DOX with redox-sensitivity was successfully synthesized for effective co-delivery of DOX, photothermal agent SWCNTs and MRI CAS gadolinium.
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