The shape effect of magnetic mesoporous silica nanoparticles on endocytosis, biocompatibility and biodistribution.

Although the aspect ratio (AR) play a crucial role in determining biological effects of homogeneous nanomaterials, studies available concerning how the shape contributes to biological effect of heterogeneous nanomaterials is limited. To systematically clarify the shape influence on the endocytosis, biocompatibility and biodistribution of magnetic mesoporous silica nanoparticles (M-MSNPs), three FITC-labeled M-MSNPs with different aspect ratio (AR=1, 2, and 4) were specifically designed and constructed through altering the ratios of CTAB/TEOS in a modified so-gel method. We have demonstrated that long-rod M-MSNP2 possessed higher intracellular internalization amount than the short-rod M-MSNP1 and the sphere-like M-MSNP0 in both cancer cells and normal cells due to the difference in the endocytosis pathways. However, there are no significant shape effects on biocompatibility including cytotoxicity and hemolytic rate. Moreover, biodistribution in HepG2 tumor-bearing mice showed that M-MSNPs administrated intravenously were mainly presented in reticuloendothelial system (RES) organs including liver, spleen and kidney. In particular, sphere-like M-MSNP0 were easily trapped in the liver, while long-rod M-MSP2 exhibited more retention in the spleen. It is worth noting that rod-like M-MSNPs are preferentially accumulated in tumor sites than sphere-like M-MSNPs, indicating an improved drug delivery efficacy in cancer therapy. Our findings may provide useful data for deeply understanding the interaction between the different shapes and biological behavior of M-MSNPs, which is expected to give rise to a new generation of heterogeneous M-MSNPs with significantly enhanced efficacy and safety for the cancer theranostics. STATEMENT OF SIGNIFICANCE: In this work, we systematically clarified the shape influence on the endocytosis, biocompatibility and biodistribution of homogeneous nanomaterials. We have demonstrated that rod-like magnetic mesoporous silica nanoparticles (M-MSNPs) were capable of higher intracellular internalization and tumor accumulation than sphere-like M-MSNPs, which was expected to give rise to a new generation of heterogeneous M-MSNPs with significantly enhanced efficacy and safety for the cancer theranostics.

Facile Synthesis of Core-shell Magnetic Mesoporous Silica Nanoparticles for pH-sensitive Anticancer Drug Delivery.

The facile synthesis of core-shell magnetic mesoporous silica nanoparticles (Fe3 O4 @mSiO2 NPs) was reported in aqueous phase using cetyltrimethylammonium bromide as a template under alcohol-free conditions. Compared to the conventional synthesis method for core-shell Fe3 O4 @mSiO2 NPs, the approach in this study is rapid (only 5-min reaction time), cheap (without using organic agents), and environmentally friendly (one-step synthesis in alcohol-free medium). Doxorubicin (DOX)-loaded Fe3 O4 @mSiO2 NPs exert extraordinarily high specificity for liver cancer cells, which was due to the pH-sensitive doxorubicin release, as well as higher endocytosis capacity in liver cancer cells rather than normal liver cells. The potential advantages of using such Fe3 O4 @mSiO2 NPs as the vehicle of anticancer drugs were that the Fe3 O4 @mSiO2 NPs exhibit good biocompatibility, high loading and protection of the guest molecules, selective killing effect, and efficient cellular uptake. The exciting pH-dependent release properties of doxorubicin-loaded Fe3 O4 @mSiO2 NPs make their use a promising strategy for enhancing efficient therapy toward tumors, while reducing the cytotoxicity of doxorubicin to human normal neutral tissue or cells.