A Research Of Nano Drug Controlled Release System Based On Mesoporous Silica

Mesoporous silica nanoparticles(MSNs) have been aroused the attention of researchers, especially in the field of medicine, because of their excellent biodegradability, stable physical and chemical properties, low toxicity, facile functionalization, tunable pore size, large pore volume and surface area. In this article, the MSNs were selected as the foundation, a series of intelligent nanocarriers have been designed and synthesized by combining the useful functions of pH-responsive, light responsive, magnetic-targeting and so on, which 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, we also summarized the synthesis methods and the functional assembly technology of the mesoporous silica drug controlled release system,investigated the drug release kinetics in detail to clarify the drug release mechanism and law. Cells experiments were used to verify the good biocompatibility, rapid cellular uptake and low cell toxicity of the drug delivery systems. The aim of this paper is to improve the diagnosis and treatment of the tumor, provide reliable data for clinical application of mesoporous silica drug controlled release system and promote the application of nanotechnology in diagnosis and treatment of major diseases.The main research contents are as follows:(1) Mesoporous molecular sieves MCM-41 was used as the host and metformin hydrochloride(MH) was used as the model drug. After modifying with cationic polymer, then PO43-/Ca2+ were added in sequence, the HAp nanoparticles can precipitate on the surface of MCM-41 as the caps. As a result of HAp in neutral or alkaline conditions remained intact and degrade in acidic condition, so MCM-41@HAp shows the pH response controlled release performance. Besides, adjust the covering amount of HAp, just by changing the number of Ca2+/PO43- adding times. The structure of the system was characterized and the drug release properties were investigated in detail.(2) First of all, upconversion nanoparticles(NaYF4 : Yb, Tm@NaYF4, named UCNPs) were introduced as core coating with mesoporous silica shell to obtain UCNP @mSiO2 core-shell nanoparticles as the host. Then, supramolecular nanovalves based on α-cyclodextrin(α-CD) torus encircle a pimelic acid thread and a photocleavable stopper(nitrobenzyl alcohol) were used as nanoscopic cap to block the pore and control the drug release. Upon irradiation of a 980 nm diode laser on UCNPs, the emitted UV light photocleaved the o-nitrobenzyl(ONB) photolabile group, causing the α-CD to dissociate from the stalk. So UCNP@mSiO2@α-CD showed a better performance of light-responsive drug controlled release. 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.(3) Firstly, the Fe3O4@mSiO2 core-shell nanoparticles were synthesized as the nanocapsules. Then, the pH-sensitive hydrazone linkage was connected to the mesoporous silica by means of chemical modification. After drug loading, the as-prepared Au nanoparticles(5 nm in size) were used as nanoscopic caps to block the pore and control the drug release. 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 good biocompatibility, magnetic-targeting and pH-responsive drug controlled release performance.