A Research Of Mesoporous Silica Nanocomposites For Drug Controlled Release

Nanotechnology, as a new technology, has been widely used in the field of medicine, it plays an extremely important role on artificial organ transplantation, medicine research and development, development of anticancer therapy and preparation of nano drug carrier etc. In this paper, we mainly study the "intelligent" nano drug delivery system based on mesoporous silica and photodynamic therapy. Because of its adjustable nano scale open channel, large pore volume, high specific surface area, controllable morphology, easy to design the surface properties and good biocompatibility, mesoporous silica were choosen as the foundation, designed and synthesized with pH, light, enzyme-sensitive targeting nano drug controlled release system. The system can transport an effective dosage of drug molecules to the targeted location, decrease collateral damage of the drug to the normal tissues and cells, enhance the bioavailability. Besides, combined with photodynamic therapy, the synergy of the two is more effective in killing tumor cells. Cell experimental results show that the nanoparticles have superior biocompatibility, rapid cellular uptake and lower cytotoxicity. Therefore, this paper studies the "intelligent" nano drug delivery system based on mesoporous silica to further promote the application of nanotechnology in the diagnosis and treatment of diseases.The main research contents are as follows:（1） Gold nanorods（GNRs） of the length to diameter ratio was 4.7 with photo thermal effect were synthesized by the seed growth method, and their surface was uniformly coated with mesoporous silica as drug carrier（GNR@mSiO₂）, modified aldehyde group on its surface, and the amino group of the anti cancer drug（DOX） is covalently bound to a pH sensitive bond, Schiff base. When the material is not to reach the tumor cells, the drug molecules can not be released and remain in the mesoporous silica channels. When it reaches the tumor cells, the acidic environment causes the cleavage of the Schiff to achieve the purpose of drug release, which plays the role of targeted therapy. At the same time, the photothermal effect of gold nanorods has made the nanocomposite to achieve a better therapeutic effect in the treatment of cancer.（2） First of all, upconversion nanoparticles NaYF₄ : Yb, Er@NaYF₄（UCNP） were introduced as core coating with photosensitizer（Ce6）-doped mesoporous silica shell（UCNP@mSiO₂/Ce6） as a drug carrier, loading anticancer drugs in the pores, coated ROS-sensitive thioketone chain as “nano gate” on its surface and modified folic acid as targeting agents. Upon irradiation of a 980 nm diode laser on UCNPs, the emitted visible light can excite the photosensitizer ROS production and break thioketone bond and the release of the drug. At the same time, the ROS can also achieve the purpose of photodynamic therapy.（3） The conversion nanoparticles NaYF₄: Yb, Tm@NaYF₄（UCNP） were synthesised by solvent thermal method, coating photosensitizer（Hypocrellin A）-doped mesoporous silica shell（UCNP@mSiO₂/HA）, loading anticancer drugs in the pores, packaged the UV-sensitive chain structure on the surface, and modified active targeting agent transferrin. Under the irradiation of 980 nm NIR light, the emitted UV light from UCNP can cause the “gate” open and release the anticancer drug. At the same time, the blue light can also achieve the purpose of photodynamic therapy. The synergistic effect of chemotherapy and photodynamic therapy is more effective in the treatment of cancer.（4） Firstly, UCNP@mSiO₂/Ce6 with visible light emission core-shell structure was synthsised as a drug carrier, after loading drug and modificating a pH and enzyme double sensitive peptide bond to encapsulate drugs, modified with transferrin for active targeting in the outer surface. The structure of the system was characterized and the drug release properties were investigated in detail. Cell experiments were used to reveal its cytotoxicity and cellular uptake etc. The multifunctional drug delivery system has been designed and synthesized by combining the useful functions of active targeting, pH and enzyme double sensitive drug controlled release performance.