Nanomedical strategy to prolong survival period, heighten cure rate, and lower systemic toxicity of S180 mice treated with MTX/MIT

Ning Song,1 Ming Zhao,1,2 Yuji Wang,1 Xi Hu,1 Jianhui Wu,1 Xueyun Jiang,1 Shan Li,1 Chunying Cui,1 Shiqi Peng1 1Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences of Capital Medical University, Beijing, People’s Republic of China; 2Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan Abstract: In spite of the usual combination form of methotrexate (MTX)/mitoxantrone (MIT) and various complex combination regimens of MTX/MIT with other anticancer drugs, the survival period, cure rate, and systemic toxicity still need to be improved. For this purpose, a nanostructured amino group-modified mesoporous silica nanoparticles (MSNN)–MTX/MIT was designed. In the preparation, the surface of mesoporous silica nanoparticles (MSNs) was modified with amino groups to form MSNN. The covalent modification of the amino groups on the surface of MSNN with MTX resulted in MSNN–MTX. The loading of MIT into the surface pores of MSNN–MTX produced nanostructured MSNN–MTX/MIT. Compared with the usual combination form (MTX/MIT), nanostructured MSNN–MTX/MIT increased the survival period greatly, heightened the cure rate to a great extent, and lowered the systemic toxicity of the treated S180 mice, significantly. These superior in vivo properties of nanostructured MSNN–MTX/MIT over the usual combination form (MTX/MIT) were correlated with the former selectively releasing MTX and MIT in tumor tissue and inside cancer cells in vitro. The chemical structure and the nanostructure of MSNN–MTX/MIT were characterized using infrared and differential scanning calorimeter spectra as well as transmission electron microscope images, respectively. Keywords: mitoxantrone, methotrexate, mesoporous silica nanoparticles, cancer therapy, nanomedicine