Synthesis And Controlled Drug Release Of Poly(Glycidyl Methacrylate)s Derivatives-hybridized Mesoporous Silica Nanomaterials

Smart drug delivery and controlled release system can enhance theeffectiveness of chemotherapy at lesion part and decrease its side effects of drugs inthe field of biomedicine. Mesoporous silica nanoparticles (MSNs) with largespecific surface area, suitable pore diameter and good biocompatibility, are idealvehicles for controlled drug release. Meanwhile, its silicon hydroxyl groups areactive and easy to be functionalized. Installing switchable molecular machinery onthe surface of nanocarriers to construct nanovalves is the critical step in thepreparation of smart drug delivery systems and preventing premature cargo release.Traditional nanovalves are mainly consisted of stalks on MSN orifices, encircled bysupramolecular macrocyclic compounds, such as cyclophanes, cyclodextrins, andcucurbiturils. In this thesis, we designed novel hybrid materials with bettercontrolled drug release behaviors by introducing polymeric materials into traditionalnanovalve systems.Azobenzene functionalized MSNs were prepared through post-syntheticmodification.-CD grafted on poly(glycidyl methacrylate)s (PGMA-CD) canencircle azobenzene through host-guest interactions to form a polymer layer on thesurface of MSNs. The resulting polymeric–organic–inorganic hybrid materials,responsive to UV-light and competitive binding agents (adamantanaminehydrochloride), exhibited better performance on encapsulation and release of cargo，as compared with traditional-type of nanovalve systems only utilizing-CDs. Inaddition, its good biocompatibility was verified by MTT assay.In order to realize zero premature release of drugs, multiple-layers ofpolymers assembled MSNs for controlled anti-cancer drug (DOX) release weredesigned. At neutral condition, diamine alkane-modified PGMA (diamino-PGMA)and CB[7] can alternately coat MSNs with negative potentials by ion-dipole interactions via layer-by-layer self-assembly technology, effectively preventing thepre-leakage of DOX from MSNs. The decrease in pH can induce the disassociationof polymer layers, leading to drug rapid release. A series of in vitro cell experimentsand in vivo tumor-growth inhibition experiments with nude mice suggested thatthese hybrid materials are ideal candidates as anti-cancer drug nanocontainers.Subsequently, diamino-PGOHMA polymer was grafted on MSNs throughcovalent bonds, whose disulfide linkages are responsive to glutathione (GSH).Meanwhile, dynamic crosslinking structure of polymer chains was formed throughthe ion-dipole interactions of CB[7] and diamine alkanes of diamino-PGOHMApolymers at neutral pH condition, and can be destroyed when the pH value wasdecreased. The cooperation of hydrogen ion and GSH caused the opening of valvesthus the release of drugs, as proven by drug release experiments.