Construction And Antitumor Studies Of Multifunctional Mesoporous Silica Co-loading Delivery System

Tumor is a serious disease threatening human health in modern society.Chemotherapy is one of the most important methods in the cancer therapy.The new tumor targeting and controlled release drug delivery system,one current research hotspot,can transport anti-tumor drugs more effectively to the lesion,which improve the anti-tumor effect and reduce systemic side effects.In this study,we used novel double-pore mesoporous silica nanoparticles to synthesis photosensitizer-doxorubicin nanocomposite with magnetic targeting,magnetic resonance imaging and pH sensitive drug release function,and also the antitumor effect of the system has been studied.Furthermore,we also studied the cell uptake ability and cytotoxicity of the novel synthesized helical or rod-like mesoporous silica nanomaterials.In the first part of the study,a facile nonpolar solvent-assisted Stober method has been developed to synthesize ordered mesoporous silica materials by uing cetyltrimethylammonium bromide as the template,tetraethyl orthosilicate as silica precursor and n-hexane as pore expanding agent in a simple aqueous-phase synthesis system.We modified the ordered mesoporous silica materials with superparamagnetic Fe3O4 through the nucleophilic substitution,using DCC as condensation agent to prepare amide linked photosensitizer Ce6 and block copolymer PAsp-b-PEG was used to improve the biocompatibility and controlled drug release of the nanocomposites.Simultaneously,the nanoparticles were loaded on the chemotherapeutic drug DOX.Thus,we designed and synthesized photosensitizer Ce6-DOX nanoparticles Ce6@MSN-Fe3O4/DOX@PAsp-b-PEG with magnetic targeting and pH controlled release ability.The DOX drug-loading of the nanoparticle was 23.67%,and the nanoparticle has obvious pH controlled release performance.under the acidic condition for 96h,the cumulative release rate of DOX is as high as 90.26%,and it has a good superparamagnetic and magnetic resonance imaging capabilities,which is potential for magnetic targeting and clinical magnetic resonance imaging.In the second part of this study,we investigated the cellular uptake ability of MSN-Fe3O4 magnetic nanoparticles and nanocomposite by biological transmission electron microscopy and fluorescence microscopy,respectively.Furthermore,flow cytometry instrument was used to measure the extracorporeal magnetic targeting photosensitizer nanocomposite,and CCK-8 method was used to examine the proliferation inhibition of drug-loading nanoparticles on B16 and MCF7/ADR cells.The results showed that the MSN-Fe3O4,Ce6@MSN-Fe3O4,Ce6@MSN-Fe3O4/DOX@PAsp-b-PEG all have good cell uptake ability.The photosensitizer nanocomposite Ce6@MSN-Fe3O4 had obvious targeting ability in vitro.The drug-loading nanoparticles had inhibitory effects on the proliferation of B16 and MCF-7/ADR cells,and the photodynamic antitumor effect in vitro may be related to the generation of reactive oxygen species.In the third part of the study,we successfully synthesized new type spiral rod-shaped mesoporous silica nanoparticles with different length-diameter ratio.Our research showed that spiral mesoporous silicas with different length-diameter ratio all have good cell uptake capacity.However,we found that the larger specific surface area prefers to have greater cell toxicity of the helical mesoporous silica rods.Besides,the level of oxidative stress was increased with the concentration.The results show that the specific surface area of the helical mesoporous silica nanoparticles may be the key factor to cytotoxicity.In summary,we successfully designed and synthesized photosensitizer Ce6-DOX nanoparticles Ce6@MSN-Fe3O4/DOX@PAsp-b-PEG with magnetic targeting and pH controlled release ability.These nanocomposites had good superparamagnetic and Magnetic Resonance Imaging ability,and also it showed good tumor cell targeting and proliferation inhibition at the cellular level.Moreover,we successfully synthesized a new type spiral rod-shaped mesoporous silica nanoparticles with different length-diameter ratio.Our research showed that spiral mesoporous silica with different length-diameter ratio has good cell uptake capacity.The increase of specific surface area of the helical mesoporous silica nanoparticles may be the key factor leading to cytotoxicity.