Construction And Properties Of New Systems For Controlled Drug Release

Traditional chemotherapeutic agents for cancers have been shown to exibit poor selectivity and strong toxicity, which limit their clinical application. Drug release triggered by internal or external stimlus can reduce toxic side effects and improve therapeutic efficacy.In a photo-controlled drug release system, the drug releases from the carrier under the irradiation of light of a specific wavelength, making spatiotemporal and quantitative controlleddrug release possible. Near-infrared light is ideal for controlled drug release due to its deeper penetration into tissue and less detriment to healthy cells. Mesoporous silica nanoparticles are excellent carriers for drug delivery due to their highly ordered mesopores, high surfaceareas, easily functionalized surface, large pore volume, andbiocompatibility. Attachment of the capping agent to the surface of mesoporous silica nanoparticles by special sensitive bond can prevent the drug leakage from the carrier while cleavage of the sensitive bond by appropriate stimlus can promote the drug release.This work mainly invloves the following two parts:1. A near-infrared light-triggered drug delivery system was constructed and its drug-releasing property was primarily invesgated.Mesoporous silica nanoparticles was used as drug carriers to load the model drug fluorescein and the photosensitizer phthalocyaninezinc. The capping agent PEG and β-cyclodextran wererespectively attached to the surface of mesoporous silica nanoparticles via siglet oxygen-sensitive thioether bond. When phthalocyanine zinc was irradiated by670nm light, singlet oxygen was produced and the thioether bond was cleaved followed by removal of the capping agent, which allowed the release of the model drug. Fluorescent detection showed that the amount of released drug increased with irradiation time.As control, the capping agent PEG was attached to the surface of mesoporous silica nanoparticles by siglet oxygen-insensitive bond. No appreciable drug release was observed under the same conditions, which further confirmed the drug release mechanism of the obove system.2. A aggregation-induced emissive compond-derived pH-sensitivedrug delivery system was constructed and its drug-releasing property was primarily invesgated.An new acidic tetraphenylethylene derivative (compound25) was synthesized. Its aggregation-induced emission property was confirmed by commonly used method. Compound25was dissolved in mixed solvent DMSO-H2O (VDMSO/VH2O=1:99). Equivalent amount of vinblastine was added and the fluorescence of the solution decreased due to the formation of the organic salt from compound25and vinblastine. When pH value of the solution was adjusted to5.5, the fluorescence increased owing to the aggregation of the freed compound25, indicating the release of vinblastine.