Fabrication Of Redox-responsive Nano-drug Delivery For Controlled Release

In recent years, the smart drug delivery systems have received tremendous attention, in particular from the field of nanomedicine. They have many advantages such as controlling the drug release rate and lowering side effect and toxicity of drugs. Among the redox-responsive nano-drug delivery systems (DDS), disulfide bond is of great interest because of its instability under the reducing glutathione (GSH). The redox-responsive nano-DDS not only tend to have increased accumulation in tumors by the passive targeting, but also avoid the premature drug leakage in the extracellular environment for the different GSH concentrations between intracellular and extracellular compartments. We synthesized two kinds of redox-responsive nano-DDS for efficient drug delivery. The main contents of this dissertation are as follows:1. A novel single-hole Glutathione (GSH)-responsive degradable hollow silica nanoparticles (G-DHSNs) were synthesized and used as carriers of doxorubicin (DOX)(DOX-G-DHSNs). The composition, morphology and properties of the G-DHSNs have been characterized by1HNMR, FTIR, TGA, TEM, and SEM. The degradation study of G-DHSNs showed that the G-DHSNs would break into pieces after interacting with GSH. Besides, the negligible hemolytic activity and low cytotoxicity of the G-DHSNs demonstrated its excellent biocompatibility. GSH-triggered release of DOX followed by the decomposition of G-DHSNs within TCA8113cancer cells was further confirmed by flow cytometry and confocal laser scanning microscopy studies.2. Two redox-responsive prodrug micellar nanoparticles (MPEG-SS-CPT) were designed and prepared by conjugating CPT onto water-soluble polyethylene glycol (PEG) via a disulfide bond. Meanwhile, the resulting MPEG-SS-CPT nanoparticles can be loaded with another drug DOX and can be accurately designed and fabricated with a simple and convenient method without any extra pernicious functionalization. Two kinds of MPEG-SS-CPT were obtained with two kinds of PEG owing different molecular weight. The MPEG-SS-CPTs have different morphology but having the same delivery behavior with GSH except the different release ratios. The cytotoxicity studies and cellular uptake studies showed that the nanoparticles exhibited an efficient cancer-targeted intracellular controlled release of the drug.