Tian Ye, Guo Ranran, Jiao Yunfeng, Sun Yangfei, Shen Shun, Wang Yajun, Lu Daru, Jiang Xingguo, Yang Wuli
State Key Laboratory of Molecular Engineering of Polymers and Department of Macromolecular Science, Fudan University, Shanghai 200433, P. R. China.
Nanoscale Horiz. 2016 Nov 17;1(6):480-487. doi: 10.1039/c6nh00139d. Epub 2016 Sep 9.
In order to specifically deliver drugs into cancer cells with targeted recognition and controlled release, biocompatible hollow mesoporous silica nanocarriers with tumor-targeting and glutathione-responsive release dual properties were developed. These multifunctional nanocarriers were fabricated by anchoring transferrin on the surface of hollow mesoporous silica nanoparticles through disulfide bond conjugation, which could be cleaved in the presence of glutathione. In this case, transferrin acted as the gatekeeper to control the drug release, and as a tumor-targeting agent to improve drug accumulation at the tumor site simultaneously. The detailed investigations indicate that the anticancer drug (doxorubicin) release from the nanocarriers was strongly dependent on the concentration of glutathione. The capacity of the nanocarriers to selectively deliver doxorubicin to the tumor cells was demonstrated in vitro and in vivo. The doxorubicin-loaded nanocarriers showed enhanced inhibition of tumor growth and minimal side-effects in vivo compared to free doxorubicin. These redox stimuli-responsive nanocarriers that achieved a combination of tumor targeting and controlled drug release provide a promising platform for efficient cancer therapies.
为了通过靶向识别和控释将药物特异性递送至癌细胞，开发了具有肿瘤靶向和谷胱甘肽响应释放双重特性的生物相容性中空介孔二氧化硅纳米载体。这些多功能纳米载体是通过二硫键共轭将转铁蛋白锚定在中空介孔二氧化硅纳米颗粒表面制备而成的，在谷胱甘肽存在的情况下二硫键可被裂解。在这种情况下，转铁蛋白充当控制药物释放的守门人，并同时作为肿瘤靶向剂提高药物在肿瘤部位的蓄积。详细研究表明，纳米载体中抗癌药物（阿霉素）的释放强烈依赖于谷胱甘肽的浓度。纳米载体将阿霉素选择性递送至肿瘤细胞的能力在体外和体内均得到了证实。与游离阿霉素相比，负载阿霉素的纳米载体在体内显示出增强的肿瘤生长抑制作用且副作用最小。这些实现了肿瘤靶向和药物控释相结合的氧化还原刺激响应性纳米载体为高效癌症治疗提供了一个有前景的平台。
