Delivering hydrophilic and hydrophobic chemotherapeutics simultaneously by magnetic mesoporous silica nanoparticles to inhibit cancer cells

Abstract

Qian Liu*, Jixi Zhang*, Wei Sun, Qian Reuben Xie, Weiliang Xia, Hongchen Gu School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, People's Republic of China*These authors contributed equally to this workAbstract: 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.Keywords: co-delivery, combination chemotherapy, doxorubicin, mesoporous nanoparticles