| In cancer therapy, drug delivery approaches have a great influence on the efficacy of drug treatments. Among the drug carriers designed for cancer therapy, layer-by-layer (LbL) microcapsules and drug delivery systems (DDSs) fabricated based on mesoporous silica nanoparticles (MSNs) have attracted a lot of attention. In this study, we designed and fabricated intelligent DDSs based on LbL microcapsules and MSNs, in order to achieve appointed exploding drug release in cancer tissues or cancer cells. The detail is displayed as follow:In chapter one, the development of LbL microcapsules and the application of LbL microcapsules in drug delivery field was introduced. Moreover, the development of MSN as drug carriers and their application in drug delivery field was also introduced according the classification of the gatekeeper.In chapter two, controllable exploding polyelectrolyte microcapsules were developed by layer-by-layer assembly of poly(allylamine hydrochloride)(PAH) and poly(sodium4-styrenesulfonate)(PSS) on a dextran microgel core containing a cleavable disulfide bond fabricated via click chemistry. Macromolecular model drug, FITC-dextran, was loaded in the microgel core. The exploding behavior of the microcapsules with an explosive release of the drug upon the injection of DTT was investigated.In chapter three, a novel intelligent "active defense" system that can specially respond to cancerous tissues for drug release was designed and prepared. The "active defense" system consists of a biodegradable dextran microgel core crosslinked by a Schiff’s base and a surrounding multilayer formed by layer-by-layer (LbL) assembly of poly(allylamine hydrochloride)(PAH) and polyaspartic acid (PASP). The loading and release of macromolecular model drug, FITC-dextran, as well as antineoplastic drug, DOX, was investigated. The in vitro cell inhibition and drug release behavior of the drug delivery system were studied and the results showed that the entrapped drug could be explosively released from the microcapsules and thereafter taken up by cancer cells upon the trigger of the acidic environment around tumor tissues.In chapter four, a novel type of cellular-uptake-shielding multifunctional envelope-type mesoporous silica nanoparticle (MEMSN) was. designed for tumor-triggered targeting drug delivery to cancerous cells.β-Cyclodextrin (β-CD) was anchored on the surface of mesoporous silica nanoparticles via disulfide linking for glutathione induced intracellular drug release. Then a peptide sequence containing Arg-Gly-Asp (RGD) motif and matrix metalloproteinase (MMP) substrate peptide Pro-Leu-Gly-Val-Arg (PLGVR) was introduced onto the surface of the nanoparticles via host-guest interaction. To protect the targeting ligand and prevent the nanoparticles from being uptaken by normal cells, the nanoparticles were further decorated with poly(aspartic acid)(PASP) to obtain MEMSN. In vitro study demonstrated that MEMSN was shielded against normal cells. After reaching the tumor cells, the targeting property could be switched on by removing the PASP protection layer via hydrolyzation of PLGVR at the MMP-rich tumor cells, which enabled the easy uptake of drug-loaded nanoparticles by tumor cells and subsequent glutathione induced drug release intracellularly. |
