功能化硼纳米双载药复合物的制备及其体外药物释放

Preparation and in vitro Drug Release of Functionalized Boron Nano Dual-loaded Drug Complex

摘要:

通过耦合热氧化蚀刻与液相剥离技术制备硼纳米片（B NSs），随后用表面活性剂（H2N-PEG-NH2）对B纳米片进行改性制备了改性聚乙二醇化硼纳米片（B-PEG），再以RGD肽（cRGD）为单体，碳二亚胺（EDC）与N-羟基琥珀酰亚胺（NHS）为引发剂制备了B-PEG-cRGD复合材料。利用B-PEG-cRGD与药物阿霉素（DOX）和热休克蛋白抑制剂烯丙胺基-17-去甲氧基格尔德霉素（17AAG）共混得到DOX-17AAG@B-PEG-cRGD纳米载药复合物。采用透射电子显微镜（TEM）、紫外分光光度计以及动态光散射仪（DLS）对B和载药复合物的形貌、结构进行了表征。结果表明，功能化硼载药复合物的流体动力学平均直径约为184 nm且具有良好的稳定性，改善了硼纳米片易聚集的缺点。体外释药研究表明，DOX-17AAG@B-PEG-cRGD复合物具有近红外光(NIR)和pH双响应性以及良好的药物缓释效果。当体外微环境pH=5.0且存在NIR时，DOX和17AAG在72 h内的累计释放率最高达66.53%和73.01%。

Abstract:

Boron nanosheets (B NSs) were prepared by coupling thermal oxidation etching and liquid exfoliation technology, and then B-PEG was prepared by modifying B NSs with surfactant (H2N-PEG-NH2). After that, the as-prepared B-PEG was used to produce B-PEG-cRGD composite by using RGD peptide (cRGD) as a monomer, ethylcarbodiimide (EDC) and N-hydroxysuccinimide (NHS) as initiators. Finally, DOX-17AAG@B-PEG-cRGD nano drug-loading complex was obtained by blending B-PEG-cRGD with the drug doxorubicin (DOX) and the heat shock protein inhibitor, allylamino-17-demethoxygeldanamycin (17AAG). The structure and morphology of B NSs and DOX-17AAG@B-PEG-cRGD composite were characterized by transmission electron microscopy (TEM), ultraviolet spectrophotometer, and dynamic light scattering (DLS). The results showed that the hydrodynamic average diameter of materials was 184 nm approximately and well dispersed. The results show that the hydrodynamic average diameter of DOX-17AAG@B-PEG-cRGD complex was 184 nm approximately and has good stability, which improves the defects of easy aggregation of B NSs. The in vitro drug release studies have shown that the complex has near-infrared light (NIR) and pH double responsiveness as well as good drug sustained release effect. When the pH value of the in vitro microenvironment was 5.0 and NIR was present, the cumulative release rates of DOX and 17AAG in 72 h were up to 66.53% and 73.01%.