Synthesis Of Amphiphilic Centipede-like Graft Polymer And Preparation Of Multifunctional Nanoparticles

In China, the development of malignant tumors has shown intensified form whichserious threat to people’s lives and health. Finding a more effective treatment ofcancer, reducing mortality and improving quality of life for patients remains grim taskfacing medicine today. In recent years, with the continuous development ofnanotechnology, nanomaterials are expected to introduce greatly improved means ofconventional cancer diagnosis and treatment. Focusing on enhancing tumor detectionefficiency and reducing the presence of conventional chemotherapy medicationvolume, the lack of specificity, side effects and other drawbacks, we use theamphiphilic polymer micelles and prepared a set of targeted, drug, drug controlledrelease detect multifunctional composite nanoparticles in this article. And theirproperties were tested.In the second chapter," Synthesis and single-function water-soluble nanoparticlesprepared by amphiphilic comb polymer PIA-PEG-DDA" we (1) using potassiumpersulfate as the initiator, with the acidic conditions and nitrogen, polyitaconic acid(PIA) was prepared by solution polymerization. FTIR and CNMR spectra proved thatit is success synthesized. And we use GPC to characterize its molecular weight (2)Make the PIA as main chain, respectively, polyethylene glycol monomethyl ethergroup (NH2-PEG2000) and dodecylamine (DDA) were connect to the polymer toprepare the amphiphilic comb-like polymer PIA-PEG-DDA. We had found the ratio of hydrophilic and hydrophobic segment when the size of the polymer micellesformed in aqueous is smallest, and under this segment ratio, morphology and criticalmicelle concentration of the polymer micelles conditions were characterized.(3) Thedrug delivery system PIA-PEG-DDA@DOX was prepared by PIA-PEG-DDA coatedthe anti-cancer drug doxorubicin. By UV spectral characteristics, we had inspected theeffects of drug release behavior in different temperature and pH conditions.(4) Usingthe coating method, the hydrophobic CdSe/ZnS quantum dots were coated by thepolymer micelles and the water-soluble fluorescent quantum dots PIA-PEG-DDA@QDs had been prepared. The acid resistance, oxidation resistance and heat resistanceof this system show that stability of nanoparticles would be greatly improved in acomplex environment by coated the amphiphilic polymer PIA-PEG-DDAIn the third chapter,"preparation of pH-sensitive targeted drug multifunctionalnanoparticles based on hydrazone bond,"(1) Due to the preparation of drug deliverysystems by coating method could not achieve drug release defects "switch" function,in Chapter2, and the drug-loaded nanoparticles would be first phagocyted into thelysosomes and endosomes which has an acidic environment with pH=5, we used thepH-sensitive hydrazone bond to connected DOX to the polymer, and prepared apH-responsive drug delivery system PIA-PEG-DDA-DOX. Tests showed that thepolymer micelle in aqueous solution has a small, uniform, monodisperse particle size.Studies also showed that the drug release characteristics under neutral conditions havesubstantially no release behavior, under acidic conditions of pH=5, the composite fitthe First-order release kinetics model Q=46.5991-45.2394e-0.24335t. Related celltoxicity tests showed that the polymeric micelles can release DOX in the acidicenvironment of phagocytosis lysosomes and endosomes, which, so as to kill the cells.(2) Useing PIA-PEG-DDA-DOX, we coated the hydrophobic nano quantum dots tandthe targeting molecules anti-VEGF were then connected which prepared the targetingpH-sensitive drug-loaded quantum dots anti-VEGF-PIA-PEG-DDA-DOX@QDs.Research shows that in aqueous solution the nanoparticle had a monodisperse and uniformity size which was32.6nm. Coated nanoparticles remain a good inheritancerelease behavior of pH-sensitive, under acidic conditions of pH=5, the composite fitthe First-order release kinetics model Q=46.7094-45.2681e-0.20123t. Cytotoxicityexperiments examined its inhibitory effect on cancer cells. Cell fluorescenceexperiments and in vivo fluorescence assay was further illustrated by comparison ofthe target molecule introducing into the composite quantum dot. By making thenanoparticles more efficient and enrichment to the solid tumor cell, it therebyachieved more rapid tumor fluorescence detection.(3) Useing PIA-PEG-DDA-DOX,we coated the hydrophobic magnetic iron oxide nanoparticles and the targetingmolecules anti-VEGF were then connected which prepared the targeting pH-sensitivedrug-loaded magnetic iron oxide nanoparticles anti-VEGF-PIA-PEG-DDA-DOX@IO. Research shows that in aqueous solution the nanoparticle had a monodisperse anduniformity size which was33.2nm. Coated nanoparticles not only remain a goodinheritance the original superparamagnetic and have a higher R2relaxation rate, itsvalue was13.1emu/g and183.6mM-1s-1. But also remain a good inheritance releasebehavior of pH-sensitive, under acidic conditions of pH=5, the composite fit theFirst-order release kinetics model Q=47.89104-41.83379e-0.23642t. Cytotoxicityexperiments examined its inhibitory effect on cancer cells. Further MRI image oftumor-bearing mice showed that the composite iron oxide nanoparticles targeted moreeffectively enrichment at solid tumor cell， which make it a highly effective MRIcontrast agent, and could significantly increase the rapid detection of tumors.In the fourth chapter,"preparation of pH-sensitive targeted drug multifunctionalnanoparticles based on the catechol borate ester bond,"(1) A pH-responsivecontrolled release model for bortezomib(BTZ) that based on Catechol borate esterbond has been constructed successfully by poly(ethylene glycol)(PEG),dodecylamine (DDA) and dopamine (DPA)-modified poly itaconic acid (PIA)(PIA-PEG-DDA-DPA-BTZ). Its structure was characterized by nuclear magneticresonance (NMR). The result showed that the targeted products were prepared successfully. The PIA-PEG-DDA-DPA-BTZ was then made into micelles. Theparticles sizes of the micelles formed by the polymer were tested by dynamic lightscattering (DLS), and observed under atomic force microscope (AFM). According tothe test, the micelles showed a spherical and monodispersed construct with very smalldiameter about35nm. The crietical micelle concentration (CMC) value was2.54×10-3mg/mL via Pyrene fluorescence method. The standard curve of BTZ wasportrayed based on the characteristic absorption peak of BTZ on300nm in UV-visabsorption. The cumulative release rates of BTZ conjugates were then studied at pH5.0and pH7.4, and the release behavior at pH5.0fit the first order kinetics model,Q=61.65866-62.13481e-0.32544t, the coefficient of determination was0.99798. The cellviability studies showed that the micelles had a quite significant inhibitory effect oncancer cells which is close to the pure bortezomib. The pH-responsive controlledrelease model has the potential of becoming a promising diagnostic tool in clinicalapplication for cancer treatment.(2) Useing PIA-PEG-DDA-BTZ, we coated thehydrophobic nano quantum dots tand the targeting molecules anti-VEGF were thenconnected which prepared the targeting pH-sensitive drug-loaded quantum dotsanti-VEGF-PIA-PEG-DDA-BTZ@QDs. Research shows that in aqueous solutionthe nanoparticle had a monodisperse and uniformity size which was41.8nm. Coatednanoparticles remain a good inheritance release behavior of pH-sensitive, under acidicconditions of pH=5, the composite fit the First-order release kinetics modelQ=61.29159-60.47169e-0.3298t. Cytotoxicity experiments examined its inhibitory effecton cancer cells. Cell fluorescence experiments and in vivo fluorescence assay wasfurther illustrated by comparison of the target molecule introducing into thecomposite quantum dot. By making the nanoparticles more efficient and enrichmentto the solid tumor cell, it thereby achieved more rapid tumor fluorescence detection.(3) Useing PIA-PEG-DDA-BTZ, we coated the hydrophobic magnetic iron oxidenanoparticles and the targeting molecules anti-VEGF were then connected whichprepared the targeting pH-sensitive drug-loaded magnetic iron oxide nanoparticles anti-VEGF-PIA-PEG-DDA-BTZ@IO. Research shows that in aqueous solution thenanoparticle had a monodisperse and uniformity size which was44.7nm. Coatednanoparticles not only remain a good inheritance the original superparamagnetic andhave a higher R2relaxation rate, its value was11.8emu/g and161.9mM-1s-1. But alsoremain a good inheritance release behavior of pH-sensitive, under acidic conditions ofpH=5, the composite fit the First-order release kinetics modelQ=60.186882-60.07816e-0.32075t. Cytotoxicity experiments examined its inhibitoryeffect on cancer cells. Further MRI image of tumor-bearing mice showed that thecomposite iron oxide nanoparticles targeted more effectively enrichment at solidtumor cell， which make it a highly effective MRI contrast agent, and couldsignificantly increase the rapid detection of tumors.