School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
Int J Nanomedicine. 2012;7:999-1013. doi: 10.2147/IJN.S28088. Epub 2012 Feb 24.
Using nanoparticles to deliver chemotherapeutics offers new opportunities for cancer therapy, but challenges still remain when they are used for the delivery of multiple drugs, especially for the synchronous delivery of hydrophilic and hydrophobic drugs in combination therapies. In this paper, we developed an approach to deliver hydrophilic-hydrophobic anticancer drug pairs by employing magnetic mesoporous silica nanoparticles (MMSNs). We prepared 50 nm-sized MMSNs with uniform pore size and evaluated their capability for the loading of two combinations of chemotherapeutics, namely doxorubicin-paclitaxel and doxorubicin-rapamycin, by means of sequential adsorption from the aqueous solution of doxorubicin and nonaqueous solutions of paclitaxel or rapamycin. Experimental results showed that the present strategy successfully realized the co-loading of hydrophilic and hydrophobic drugs with high-loading content and widely tunable ratio range. We elaborate on the theory behind the molecular interaction between the silica hydroxyl groups and drug molecules, which underlie the controllable loading, and the subsequent release of the drug pairs. Then we demonstrate that the multidrug-loaded MMSNs could be easily internalized by A549 human pulmonary adenocarcinoma cells, and produce enhanced tumor cell apoptosis and growth inhibition as compared to single-drug loaded MMSNs. Our study thus realized simultaneous and dose-tunable delivery of hydrophilic and hydrophobic drugs, which were endowed with improved anticancer efficacy. This strategy could be readily extended to other chemotherapeutic combinations and might have clinically translatable significance.
利用纳米颗粒输送化疗药物为癌症治疗提供了新的机会，但在用于输送多种药物时仍存在挑战，尤其是在联合治疗中同时输送亲水性和疏水性药物时。在本文中，我们开发了一种利用磁性介孔硅纳米颗粒（MMSNs）输送亲水性-疏水性抗癌药物对的方法。我们制备了具有均匀孔径的 50nm 大小的 MMSNs，并通过从阿霉素水溶液和紫杉醇或雷帕霉素的非水溶液中顺序吸附来评估它们对两种化疗药物组合，即阿霉素-紫杉醇和阿霉素-雷帕霉素的负载能力。实验结果表明，本策略成功地实现了高载药量和广泛可调比例范围的亲水性和疏水性药物的共载。我们详细阐述了硅羟基与药物分子之间分子相互作用的理论基础，这是可控负载的基础，也是随后药物对的释放。然后，我们证明了多药物负载的 MMSNs 可以很容易地被 A549 人肺腺癌细胞内化，并产生比单药物负载的 MMSNs 更强的肿瘤细胞凋亡和生长抑制作用。因此，我们的研究实现了亲水性和疏水性药物的同时和剂量可调输送，赋予了它们增强的抗癌功效。该策略可以很容易地扩展到其他化疗药物组合，并且可能具有临床转化意义。
