Fabrication of doxorubicin-loaded monodisperse spherical micro-mesoporous silicon particles for enhanced inhibition of cancer cell proliferation

Abstract

Spherical micro-mesoporous silicon (mSi) particles were fabricated by thermal decomposition of monosilane (SiH4) within the mesopores of monodisperse silica particles (MSP) and subsequent etching out of the template material. The thermal destruction of SiH4 occurs within the whole pore volume uniformly because in the thermal chemical vapor deposition method we developed, the limiting stage of the process in which MSP pores are filled with silicon is the reaction in which monosilane is decomposed, rather than its diffusion within template mesopores. The porosity of the mSi particles synthesized can be varied without changes in the shape and outer diameter of the particles by varying the parameters of the technological process of silane decomposition. The particles have large Brunauer-Emmett-Teller specific surface area (250–350 m2 g−1) and pore volume (0.3–0.5 cm3 g−1). For the first time the obtained submicron spherical porous silicon particles are monodisperse with a size scatter not exceeding 10%, which provides the identity of their hydrodynamic and adsorption properties so important for biomedical applications. We introduced the cytostatic drug doxorubicin (DOX) into mSi pores by the physical adsorption method. It was shown that DOX is desorbed from the mSi pores and penetrates into K-562 cancer cells, with local DOX concentration maxima observed in the intracellular space. The cytotoxicity of the mSi and mSi/DOX particles was studied, and the inhibition capacities of the cancer-cell proliferation by doxorubicin adsorbed by mSi particles and a DOX solution were compared in vitro. It was shown that the half-maximal inhibitory concentration (IC50) is four times lower under the action of DOX-loaded mSi particles as compared with free doxorubicin.