Guo Chunhua, Hu Jiani, Kao Leslie, Pan Dayi, Luo Kui, Li Ning, Gu Zhongwei
Department of Radiology, Wayne State University, Detroit, Michigan 48201, United States.
ACS Biomater Sci Eng. 2016 May 9;2(5):860-870. doi: 10.1021/acsbiomaterials.6b00093. Epub 2016 Apr 12.
In this study, we designed and fabricated a nanohybrid of mesoporous silica nanoparticles (MSNs) functionalized with peptide dendrons and evaluated its potential biocompatibility. The nanohybrid was prepared by combining azido-MSNs with alkynyl peptide dendrons via click chemistry to improve graft ratio. By modifying the azido-MSNs through the addition of the alkynyl peptide dendrons, we amplified and broadened the scope of their applications. After labeling with Cy5.5 dye, the nanohybrid was characterized by transmission electron microscopy (TEM), thermogravimetric analysis (TGA), nitrogen adsorption-desorption isotherms, dynamic light scattering (DLS) and zeta potential. The resulting nanohybrid showed high mono-dispersivity with a spherical diameter of 60 nm, negative surface charge and aqueous environment stability. Finally, a systematic assessment was conducted to evaluate the biocompatibility of the MSN-dendron-Cy5.5-based nanohybrid, both in vitro and in vivo. Cytotoxicity measurements, body weight shifts, histological analysis, and routine blood tests with mice demonstrated that the nanohybrid had good biocompatibility. Hemocompatibility evaluations demonstrated that the nanohybrid had improved blood safety compared to bare MSNs. Healthy nude mice were used to analyze the in vivo optical fluorescence images. Ex vivo fluorescence images of the major organs were studied to further evaluate the in vivo biodistribution of the nanohybrid, with results suggesting that the MSN-dendron-Cy5.5-based nanohybrid provided promise in biomedical applications. Overall, we provided a preliminary but important research piece on the safety and efficiency of MSN-dendron-Cy5.5-based nanohybrid as an in vivo functional vehicle used in diagnosis and therapy.
在本研究中,我们设计并制备了一种用肽树枝状分子功能化的介孔二氧化硅纳米颗粒(MSN)纳米杂化物,并评估了其潜在的生物相容性。通过点击化学将叠氮基MSN与炔基肽树枝状分子结合来制备纳米杂化物,以提高接枝率。通过添加炔基肽树枝状分子对叠氮基MSN进行修饰,我们扩大并拓宽了其应用范围。用Cy5.5染料标记后,通过透射电子显微镜(TEM)、热重分析(TGA)、氮吸附-脱附等温线、动态光散射(DLS)和zeta电位对纳米杂化物进行了表征。所得纳米杂化物显示出高单分散性,球形直径为60nm,表面带负电荷且在水性环境中稳定。最后,进行了系统评估以评价基于MSN-树枝状分子-Cy5.5的纳米杂化物在体外和体内的生物相容性。对小鼠的细胞毒性测量、体重变化、组织学分析和常规血液检测表明,该纳米杂化物具有良好的生物相容性。血液相容性评估表明,与裸露的MSN相比,该纳米杂化物的血液安全性有所提高。使用健康的裸鼠分析体内光学荧光图像。研究主要器官的离体荧光图像以进一步评估纳米杂化物的体内生物分布,结果表明基于MSN-树枝状分子-Cy5.5的纳米杂化物在生物医学应用中具有前景。总体而言,我们提供了一项关于基于MSN-树枝状分子-Cy5.5的纳米杂化物作为用于诊断和治疗的体内功能载体的安全性和效率的初步但重要的研究成果。