Janus Silver-Mesoporous Silica Nanocarriers For Cancer Theranostics

Current conventional chemotherapeutic inevitably causes damage to normal cells due to poor targeting and limits the clinical application. With the continuous development of nanomedicines, more and more areas of nanomaterials focused on the cancer treatment. In recent years, mesoporous nanomaterials was considered as the effective carriers, which delivered drugs directly to the tumor site and reduced the side effects. In the meanwhile,the release of real-time tracing can also showed caner treatment effect. Among nanomaterials, silver- advantages mesoporous silica nanoparticles(Ag-MSN) due to their drug loading capacity, surface-enhanced Raman scattering, biocompatibility, and easy surface modification, etc., caused domestic wide attention outside researchers, since the conventional core-shell structure of silver-small mesoporous silica nanoparticle drug content, surface enhanced Raman scattering(SERS) effect is poor, further limiting its use as a versatile drug carriers.Therefore, the development of silver having a new structure- mesoporous silica nanoparticles versatile drug carriers in favor of the development of cancer diagnosis and therapy. On this basis, this paper intends to synthesize silver asymmetric structure- based mesoporous silica nanoparticles, based on a preliminary discussion of the mechanism of asymmetric synthesis of nanoparticles to study the endocytosis and toxic effects at the cellular level, further testing its carrying value and p H-responsive release of doxorubicin role and enhance the SERS effect in vitro studies and selective anti-tumor effect.Purpose:By optimizing the reaction conditions for the synthesis of Janus type silver-mesoporous silica nanoparticles(J-Ag-MSN), and to investigate its characterization of asymmetric synthesis mechanism; research on Janus type silver- mesoporous silica nanoparticles(J-Ag-MSN) endocytosis and toxicity profiles; explore by UV spectrophotometer equipped with doxorubicin(DOX) and the amount of thep H-responsive releasing effect release of the drug, study(J-Ag-MSN-DOX) in vitro enhanced SERS effect and anti-tumor effects were studied, and its end as a chemotherapeutic drug carriers for tumor diagnosis and integration provides a theoretical basis.Research contentsBy transmission electron microscopy electron microscopy, scanning electron microscopy electron microscopy, Nano ZS laser particle size analyzer, BET surface area, UV- visible spectroscopy and X-ray diffraction analysis were morphology and physicochemical and optical properties of J-Ag-MSN were characterized, and to investigate the mechanism of asymmetric synthesis by transmission electron microscopy electron microscopy. Human hepatoma Hep G2 cells and normal human HL-7702 cells for the study, to detect the impact J-Ag-MSN on cell activity by SRB assay, confocal fluorescence microscopy and flow cytometry J-Ag-MSN cells by laser endocytosis amount; doxorubicin(DOX) as a template drugs Spectrophotometric J-Ag-MSN carrying amount of DOX and DOX release of p H-responsive performance through UV spectrophotometry; and laser confocal fluorescence microscopy and flow to probe J-Ag-MSN-DOX tumor cells release the role; on this basis, the study of J-Ag-MSN-DOX enhanced tumor cells by Raman SERS effect imager, and by SRB Study J-Ag role-MSN-DOX selective killing of tumor cells.Methods and Results1. By changing the reaction conditions, we successfully synthesized asymmetric structure of silver- mesoporous silica nanoparticles(J-Ag-MSN), after Morphology Characterization of proved J-Ag-MSN ball rod-like structure morphology was homogeneous, one end 100 nm spherical silver nanoparticles, the other end is approximately 200-300 nm long mesoporous silica rods, further characterization of physical and chemical properties confirmed J-Ag-MSN has a better mesoporous nature and effect of surface plasmon resonance, comprising the SERS enhancements.2. within endocytosis experiments showed J-Ag-MSN can endocytosis into the Hep G2 tumor cells and normal cells HL-7702, and the amount of endocytosis into tumor cells more than normal cells; cytotoxicity assays show that 24 and 48 h at JAg-MSN on Hep G2, A549, and HL-7702, HUVEC, BMSCs normal activity of cells MCF-7 tumor cells were not affected.3. J-Ag-MSN can be supported DOX, drug experiments show that its drug was10.6% encapsulation efficiency was 63.9%, the release experiments showed J-Ag-MSN-DOX solution at p H = 5.5 96 h in vitro release rate is about 40% higher than p H = 5.5 when the release rate of 5%; further studies showed J-Ag-MSN-DOX in Hep G2 cells release more than the HL-7702 cells.4. Raman cell imaging experiments showed that Hep G2 cells, J-Ag-MSN-DOX DOX can be enhanced Raman imaging, the realization of tumor cells SERS imaging results.5. Cytotoxicity experiments showed J-Ag-MSN-DOX selectively killing Hep G2,A549, MCF-7 tumor cells and can weaken, BMSCs toxic effects of DOX for HL-7702, HUVEC normal cells.Conclusion1. We use a modified version of the sol- gel method for the preparation of successful cooperation asymmetrical shape silver uniform- mesoporous silica nanoparticles(J-Ag-MSN), which have excellent properties of SERS and mesoporous.2. Can endocytosis into tumor cells in the amount of J-Ag-MSN than normal cells,and for a variety of cells have good biological safety.3. J-Ag-MSN can be supported DOX chemotherapy drugs and in vitro and in cells to achieve a p H-responsive release of the drug, J-Ag-MSN-DOX also selective towards tumor cells SERS imaging and tumor cells while killing DOX reduced toxicity to normal cells.