Preparation,Characterization And Application Of Multfunctional Luminescene/magnetic Nanomter Drug Carriers

With the rapid development and organic integration of materials science, chemistry, life sciences, pharmacy and medical science, as a branch of nanoscale science and technology, the nanometer drug carrier has exhibited extensive application prospects in diagnosis, prevention and treatment of disease, and plays an important role in the development of medicine. This paper started from studying the active ingredients and effect mechanism of diet supplements, and presented three kinds of synthesis approaches of multifunctional nanometer drug carriers with tracing and targeting properties using modified or raw chitosan as matrixes for peptides drug (insulin), hydrophilism drug (adriamycin), and hydrophobicity drug (camptothecin) delivery, respectively. The more detailed novelty of this research can be categorized as following:1. The cell membrane stationary phase (CMSP) was prepared by immobilizing rat islet pancreas cell membrane on the surface of silica. The resulting CMSP was filled into chromatographic column with enzymatic activity, stability and reproducibility. The dissociation constant (Kd) and the amount of active binding sites (B,) for mangiferin (MF) on cell membrane were determined using frontal chromatography. The results suggested that mangiferin possessed strong affinity with membrane protein and abundant binding sites on cell membrane, which provided powerful evidence for regulatory function of mangiferin on insulin signaling pathway.2. The interaction properties of active compounds in green tea extract (GTE) and involved proteins in the path of drugs delivery were studied systematically by high performance liquid chromatography-UV/DAD combined with ultrafiltration. The results showed that (-)-epigallocatechin gallate (EGCG) and (-)-epicatechin gallate (ECG) were main active components in GTE. There were high binding degrees between two catechins and transportation proteins in plasma, and proteins on cell membrane. We suggest that the inhibition of the pathogenesis of some diseases (diabetes mellitus and cancer) by green tea should be associated with the high affinities of catechins to transportation proteins and cell membrane proteins. 3. The chitosan-based luminescent/magnetic (CLM) hybrid nanogels were synthesized with different chitosan/QD/MNP ratios and under different processing parameters by direct gelation of chitosan, CdTe and superparamagnetic iron oxide into the copolymer. Spherical CLM hybrid nanogels possessed appropriate average sizes (＜160nm) and moderate loading amount of insulin (40.1mg/g). Human normal hepatocytes L02cell line was used to explore the effects of additives, such as MF, EGCG, and ECG on the insulin-receptor-mediated cellular uptake using insulin-loaded CLM hybrid nanogels. The study demonstrates that MF, EGCG and ECG are potentially able to enhance targeting combination of insulin with L02cells and improve insulin sensitivity in L02cells, which provide directly evidence for antidiabetic activity of above three components and expand the potential application for the nano drug carrier.4. A novel folate conjugated carboxymethyl chitosan-ferroferric oxide doped cadmium telluride quantum dot nanoparticles (abbreviate:CFLMNPs) was developed by assembly in situ. The as-prepared CFLMNPs possessed intense superparamagnetic and fluorescent property at room temperature. The size range of CFLMNPs was about170-190nm. The loading efficiency and cumulative release of anticancer drug (adriamycin, ADM) on the CFLMNPs were determined. The CFLMNPs were transported into the HepG2cells by an folate-receptor-mediated endocytosis mechanism. The results indicate that the multifunctional CFLMNPs possess a high drug loading efficiency, low cytotoxicity and favourable cell compatibility, and are promising candidates for carboxymethyl chitosan-based targeted drug delivery and cellular imaging.5. A novel chitosan-based luminescent/magnetic hybrid nanoparticles with folate-conjugated tetrapeptide composites (CLMNPs-tetrapeptide-FA) was synthesized by direct gelation combined with conjugation in situ. The size range of CLMNPs-tetrapeptide-FA copolymers was approximately150-190nm. The folate-tetrapeptide pocket-like structures designed specifically for targeting and loading camptothecin (CPT) could prevent CPT from hydrolyzation and toxicity diffusion to some extent. Additionally, the loading amount of CPT could be regulated by conjugating different hydrophobic peptide on copolymer, which is a kind of new concept having both drug loading and drug protecting. Dual specific targeting of the copolymers to cancer cells was achieved under external magnetic field guidance combined with a folate-receptor-mediated endocytosis. The multifunctional CLMNPs-tetrapeptide-FA copolymers are promising candidates for tumor-targeted drug delivery.