Preparation Of Multifunctional Gene Vectors Based On Quantum Dots

Gene therapy is promising as the treatment of human disease including congenital genetic defects and acquired diseases. The gene vector with high transfection and low toxicity is a premise for clinical practice. Quantum dots (QDs) possess long-term photostability, high photoluminescence quantum yields, as well as size-tunable and narrow-band emissions, which made QDs emerge as ideal fluorescence probes to track important biological processes. Multifunctional nanoparticles provide the potential opportunity for combined real-time imaging and cancer therapy by integrating two or more different imaging modalities into a single nanoplatform. Thus, we constructed combined gene vectors based on QDs which could integrate diagnosis and therapy within one nanostructure.The main work is summarized as follows:1. The size, shape and surface functional groups of nanoparticles would significantly influence their behaviors in biological systems. In this work, we constructed QDs encapsulated in silica (QDs@SiO2) with different morphologies and discussed the difference in gene transfection and celluar internalization caused by morphologies. We first exploited a facile route to synthesize 1D wormlike QDs@SiO2 nanocomposites with controlled aspect ratios, where the multiple QDs arranged in the center line of nanoparticles. Such well-defined 1D QDs@SiO2 nanoparticles were simply achieved by controlled hydrolysis and polycondensation of tetraethyl orthosilicate (TEOS) employing NH4OH as the catalyst. Then, BUCT-PGEA (ethanolamine-functionalized poly(glycidyl methacrylate)) brushes were in-situ prepared via atom transfer radical polymerization (ATRP) on the outer surfaces of QDs@SiO2 nanoparticles, resulting in QDs@SiO2-PGEA nanohybrids with different aspect ratios for biomedical applications. It is expected that such obtained nanoparticles would exhibit nice performance as gene carriers and monitor the delivery process, especially for long-term tracking. The effects of the morphologies of the carriers on gene transfection were also investigated. The longer wormlike nanoparticles exhibited best gene transfection performance. By taking advantage of favorable optical properties of the encapsulated QDs, the process of gene delivery was also well tracked in real time.2. Multimodal imaging and combined therapy would make cancer therapy more precise and effective. In this work, we synthesized gold nanorods (Au NR) encapsulated into silica with the modification of QDs on the surface, denoted as Au NR@SiO2-QDs (ASQ). Subsequently, we designed multifuntical ASQ-PGEA with the supramolecular gatekeeper induced by near-infrared light (NIR). The results demonstrated that the gene transfection of ASQ-PGEA was much higer than cyclodextrin-PGEA (CD-PGEA). Moreover, ASQ-PGEA with doxorubicin (DOX) loading (ASQ-PGEA-DOX) could deliver tumor-suppressor gene p53 into the cell and the elevated temperature induced by NIR caused the dissociation of CD-PGEA. Thus, the DOX would be released and lead to the cell apoptosis. The system combined gene therapy, photothermal therapy and NIR-activated chemotherapy into a single structure with excellent antitumous effect. Owing to the optical properities of Au NR and QDs, the combined imaging of computed tomography (CT), photoacoustic (PA) and fluorescence (FL) imaging was realized.