Multimodal Imaging And Enhanced Chemotherapy For Breast Cancer Based On Mesoporous Organosilica

Breast cancer is the most common malignant tumor in women and one of the leading causes of death in women.Therefore,early detection and early treatment are urgent.Traditional breast cancer imaging and treatment models have many limitations such as lack of targeting.Nanomaterials have provided new imaging methods for breast cancer in biomedical applications.Mesoporous organosilica have good dispersion,uniform size,large specific surface area,excellent biocompatibility and EPR effect.As it is better able to stagnate in the tumor,it is a good vehicle for tumor imaging and treatment systems.In addition,the organosilica can be modified by an organic group and can selectively modify and combine a plurality of imaging modes with the target polypeptide.In this thesis,mesoporous organosilica was used to study the effect of chemotherapy and multimodality imaging in breast cancer.1、Synergistic chemotherapy of multi-resistant breast cancer cells based on mesoporous organosilica nanorods with different aspect ratiosIn the work,we developed a nano-platform with adjustable aspect ratio for multi-resistant breast cancer cells for enhanced chemotherapy.Firstly,small size thioether-bridged mesoporous organosilica nanorod(MONRs)are successfully synthesized using cetyltrimethylammonium bromide(CTAB)as structure-directing agent and bis[3-(triethoxysilyl)propyl]tetrasulfide(TETS)and tetraethoxysilane(TEOS)as co-precursors.The MONRs have tunable aspect ratios of 2,3,and 4(denoted as MONRs-2,MONRs-3,and MONRs-4),small and controllable lengths(75-310 nm),high surface area(570-870 cm2 g-1),uniform mesopores(2.4-2.6 nm),large pore volume(0,34 cm3 g-1),and excellent biocompatibility.The uptake of the MONRs by multidrug resistant human breast cancer MDR-MCF-7 cells is related to their aspect ratios.The MONRs-3 shows a faster and higher cellular internalization compared to the MONRs-4 and MONRs-2,respectively.At the same time,chemotherapy results showed a significant increase in MONR chemotherapy with doxorubicin(DOX).And,thanks to the high cellular uptake,doxorubicin(DOX)loaded MONRs-3 show obviously improved chemotherapeutic effect on MDR-MCF-7 cancer cells.Therefore,MONR nano-platform in the treatment of multi-resistant breast cancer has great potential.2、Targeted bimodal imaging of multiple triple-negative breast cancer based on mesoporous organosilica.A targeted nanoplatelet probe with near-infrared fluorescence and magnetic resonance dual mode imaging modalities was developed for imaging nude mice vaccinated with three negative breast cancer cells.In this work,bis[3-(triethoxysilyl)propyl]tetrasulfide(TETS)and hexamethyldisilazane Tetraethoxysilane(TEOS)as a copolymer,cetyltrimethylammonium bromide(CTAB)as structure-directing agent,organic mesoporous organosilica nanoparticles(MONs)were constructed,and then near-infrared fluorescence(NIRF)dye maleimide derivative cyanine dye(Mal-Cy5.5),RGD targeting peptide(Mal-PEG2-RGD(CRGDKGPDC))and Mal-PEG2-NH2 which is containing amino was contacted on the mesoporous organosilica(MONs)by click reaction,and finally the carboxyl group of magnetic resonance contrast agent Gd-DTPA was conjugation to nanoparticle MON-NH2-Cy5.5-RGD through a condensation reaction.The obtained nanoparticle(MON-NH2-Cy5.5-RGD-Gd)has a good stability,excellent biocompatibility,dual-mode imaging ability of magnetic resonance(MR)and near infrared fluorescence(NIFR),and has the characteristics of targeting breast cancer cells in vitro.Our results show that the properties of MR and NIFR based on mesoporous organosilica nanoparticles(MONs)contribute to the potential for targeting breast cancer imaging.