Self-Assembled Nanoparticles Applied In Cell Imaging And Grug/Gene Delivery

We mainly studied the self-assembled nanoparticles applied in cell imaging and drug/gene delivery. The main content and conclusion of this dissertation were summarized below:(1) We designed and synthesized an amphiphilic supermolecule recognition motif with peptides fragment and quaternary ammonium groups. From dynamic light scattering assays and transmission electro microscopy pictures, it was founded that amphiphilic pillar[5]arene ten-substituted were able to form micelles in aqueous solution. Zeta potential of the amphiphilic nanoparticles was 30 mV, showing that they could tightly condense negatively charged DNA. UV-visible spectrum were utilized to study the changes of absorption spectrum. It was founded that there really were great changes before and after DNA condensed, showing that electrostatic reaction did happen between supramolecular nanoparticles and DNA. Furthermore, the particle size became smaller after DNA condensed, this may be DNA loading could compress loose vesicle structure at some extent and encourage them to move to a more stable structure, further proving apillar[5]arene ten-substituted could stably complex DNA biological macromolecules.(2) An unsymmetric N3C2/BF2 organic fluorophore P3T was designed and synthesized. P3T exhibited an ICT effect caused by the donor-acceptor interaction between the quinoline group and the aniline unit. Whereas it emitted faintly in solution, it became highly emissive in the aggregated state, demonstrating an attracting phenomenon of aggregation-induced emission. It was highly sensitive to intra-and extra-cellular pH changes. The emission of P3T was quenched completely after it was uptaken by HeLa cells due to the protonation of N,N’-dimethylamine group. Furthermore, P3T and DOX were encapsulated into the hydrophobic core of PF127 to construct a FRET system, where P3T acted as the donor and DOX as the acceptor. This ternary system also turned out to be a smart drug delivery system. It not only could realize controlled drug release, but also remain its therapeutic effect of DOX towards the cancerous HeLa cells. Absolutely, this new AIEgen with high sensitivity to intra- and extra-cellular pH changes will not only enrich the family of AIEgens and find wide application in chemosensors and bioprobes etc., but also attract considerable attentions from scientists in the areas of fundamental photophysical research and material sciences.(3) We established a new host-guest recognition motif among big cavity CB[8], electron-rich PEG-Np and electron-deficient Paraquat. Based on this newl molecular recognition motif, an amphiphilic supramolecular triblock copolymer (CB[8](?) (mPEG-Np·PTPE)) was fabricated with the mPEG-Np segment as the hydrophilic part and the polymer PTPE segment as the hydrophobic section. CB[8](?)(mPEG-Np·PTPE) self-assembled to micelle in water, which were utilized to encapsulate anticancer drug DOX. Furthermore, we constructed a FRET system, where PTPE acted as the donor and DOX as the acceptor. Due to the FRET effect which occurred between donor and receptor and the ACQ effect of DOX, the fluorescence of micelles was quenched. But after dissociation of micelles in reduction condition, the fluorescence will be restored. The nanoparticles exhibited reduction-triggered disassembly, resulting in the release of the anticancer drug. In vitro experiments show that micelles exhibited low cytotoxicity and could simultaneously realize pH and reduction response. What’s more, the blue fluorescence of PTPE overlapped well with red fluorescent of DOX, so it can precisely trace the process of drug release. In vivo experiments demonstrated that DOX-loaded micelles exhibited enhanced accumulation in tumor tissue, dramatically higher antitumor effect and lower systematic toxicity than free DOX in the HeLa tumor xenograft-bearing nude mice.