Zhou Mengyun, Du Xin, Li Weike, Li Xiaoyu, Huang Hongwei, Liao Qingliang, Shi Bingyang, Zhang Xueji, Zhang Meiqin
Research Center for Bioengineering and Sensing Technology, Beijing Key Laboratory for Bioengineering and Sensing Technology, School of Chemistry and Biological Engineering, University of Science & Technology Beijing, Beijing 100083, P. R. China.
J Mater Chem B. 2017 Jun 21;5(23):4455-4469. doi: 10.1039/c6tb03368g. Epub 2017 Feb 8.
Biodegradability is very critical for biomaterials to be nanocarriers. Ideal nanocarriers should be stable enough to execute their functions, but then can be efficiently got rid of, by either biodegradation or excretion. In this work, we report the design and one-pot fabrication of a series of uniform organic-inorganic hybrid nanocapsules with a disulfide-bridged silsesquioxane framework and a particle size smaller than 100 nm for redox-triggered biodegradation. The optimal synthesis conditions were explored for balancing the nanostructure, sulfur (S) content and aggregation degree. Fluorescent molecules were also integrated into the disulfide-bridged silsesquioxane framework by a co-condensation strategy for fluorescence tracking. Dithiothreitol (DTT) as a strong model reducing agent triggered the breakdown of hybrid nanocapsules without and with PEG modification from intact nanospheres to small fragments, while intracellular glutathione (GSH) had a slightly lower capacity of biodegrading these nanocapsules. The constructed delivery system obviously inhibited the growth of A549 cancer cells due to efficient cellular uptake by an endocytosis pathway and the subsequent pH and GSH-triggered drug release. The possibility of regulating the framework and surface functionalization of hybrid nanocapsules opens new opportunities for the development of silica-based degradable hybrid nanocarriers for promising drug delivery.
生物可降解性对于作为纳米载体的生物材料而言至关重要。理想的纳米载体应足够稳定以执行其功能，但随后能够通过生物降解或排泄被有效清除。在本工作中，我们报道了一系列具有二硫键桥联倍半硅氧烷骨架且粒径小于100 nm的均匀有机 - 无机杂化纳米胶囊的设计与一锅法制备，用于氧化还原触发的生物降解。探索了用于平衡纳米结构、硫（S）含量和聚集程度的最佳合成条件。还通过共缩合策略将荧光分子整合到二硫键桥联倍半硅氧烷骨架中用于荧光追踪。作为强模型还原剂的二硫苏糖醇（DTT）触发了未修饰和经聚乙二醇（PEG）修饰的杂化纳米胶囊从完整纳米球分解为小片段，而细胞内谷胱甘肽（GSH）对这些纳米胶囊的生物降解能力略低。构建的递送系统由于通过内吞途径的有效细胞摄取以及随后的pH和GSH触发的药物释放，明显抑制了A549癌细胞的生长。调节杂化纳米胶囊骨架和表面功能化的可能性为开发用于有前景的药物递送的基于二氧化硅的可降解杂化纳米载体开辟了新机遇。
