Zhu Junxiao, Guo Xiaoxi, Guo Tingting, Yang Ye, Cui Xiuming, Pan Jun, Qu Yuan, Wang Chengxiao
Faculty of Life Science and Technology, Kunming University of Science and Technology Kunming 650500 China
Key Laboratory of Sustainable Utilization of Panax Notoginseng Resources of Yunnan Province Kunming 650500 China.
RSC Adv. 2018 Dec 3;8(70):40308-40320. doi: 10.1039/c8ra07202g. eCollection 2018 Nov 28.
In this investigation, innovative pH-sensitive and amphiphilic nanoparticles (NPs) were synthesized by grafting histidine (His, pH sensitive molecule) and stearic acid (SA, hydrophobic segment) onto the polysaccharides of (BSP). The His-SA-BSP was able to self-assemble into NPs with pH sensitivity. The acidic conditions could trigger the imidazole ionization and reverse the surface charge, while the electrostatic repulsion wrecked the structure and drove the NPs to a swollen state, as revealed by dynamic light scattering (DLS), transmission electron microscopy (TEM), and critical micelle concentration (CMC) analyses. By increasing the degree of substitution (DS) of His, the NPs showed improved pH sensitivity. The NPs could accelerate Doxorubicin (Dox) release to a remarkably greater extent (3-fold) at pH 5 than at pH 7.4. The CCK-8 assay demonstrated a good biocompatibility of the NPs towards different cell lines and a specific inhibition effect of Dox-loaded NPs against tumor cells. Furthermore, the NPs showed the improved cellular uptake of Dox towards MCF-7 by fluorescence microscopy and flow cytometry. Therefore, the new His-SA-BSP showed potential applications in drug nanocarrier systems.
在本研究中，通过将组氨酸（His，pH敏感分子）和硬脂酸（SA，疏水链段）接枝到（BSP）的多糖上，合成了具有创新性的pH敏感两亲性纳米颗粒（NPs）。His-SA-BSP能够自组装成具有pH敏感性的纳米颗粒。酸性条件可引发咪唑离子化并使表面电荷反转，而静电排斥破坏了结构并使纳米颗粒进入肿胀状态，动态光散射（DLS）、透射电子显微镜（TEM）和临界胶束浓度（CMC）分析表明了这一点。通过增加His的取代度（DS），纳米颗粒表现出更好的pH敏感性。纳米颗粒在pH 5时比在pH 7.4时能更显著地加速阿霉素（Dox）释放（3倍）。CCK-8测定表明纳米颗粒对不同细胞系具有良好的生物相容性，且载有Dox的纳米颗粒对肿瘤细胞具有特异性抑制作用。此外，通过荧光显微镜和流式细胞术显示纳米颗粒提高了Dox对MCF-7细胞的摄取。因此，新型His-SA-BSP在药物纳米载体系统中显示出潜在应用。
