Synthesis Of Functional Polymers And Study Of Targeting Drug Loading Nanoparticles

The integration of nanotechnology with molecular biology and medicine has resulted in active developments of a new emerging research area, nanobiotechnology,1 which offers exciting opportunities for discovering new materials, processes, and phenomena. Semiconductor quantum dots (QDs) are emerging as a new class of fluorescent labels for molecular, cellular, and in-vivo imaging applications, due to their narrow and size-tunable emission spectra, broad absorption profiles, and superior photostability.Nanoscale magnetic materials have their own advantages that provide many exciting opportunities in biomedical applications. First, they deliver controllable sizes ranging from a few up to tens of nanometers, so their optimization of sizes and properties easily matches with the interest of study. Second, the nanoparticles can be manipulated by an external magnetic force. Third, magnetic nanoparticles play an important role as MRI contrast enhancement agents because the signal of magnetic moment of a proton around magnetic nanoparticles can be captured by resonant absorption. Recently, the active explorations of the applications of nanoparticles have advanced considerably, including biomedicine.The development of multifunctional nanoparticles that have dual capabilities of tumor imaging and delivering therapeutic agents into tumor cells holds great promises for novel approaches for tumor imaging and therapy. In this paper, the multi-carboxyl copolymers and the multifunctional comb amphiphilic copolymers are synthesized, the properties and structure of the copolymers are studied. Using these copolymers, water soluble nanoparticles are prepared by different methods, at the same time, the properties of the nanoparticles are studies. In addition, we prepared the nanoparticles drug loading vehicles with multifunction of imaging, targeting and drug delivery, and their properties and the application in tumor imaging and therapy were studied.In Chapter 1, we firstly described the research progress and the synthesis of the amphiphilic copolymer. Next, we expounded the properties, synthesis and application of the luminescent nanoparticles and the magnetic nanoparticles. At last, we introduced the preparation, properties and application of the multifunctional nanoparticles drug loading vehicles.In Chapter 2, the itaonic Acid/methylacrylate copolymer, PIA-MAA, obtaining multi-carboxyl was synthesized using solution copolymerization, and we studied the influence of different reaction conditions on the viscosity-average molecular weight. The control of the copolymer's molecular weight was realized by detecting the influence of reaction conditions on Mη, including monomer molar ratio, reaction time, tempature and initiator dosage. The PIA-MAA was used to replace the organic alkylamine ligands coated on CdSe/CdS core-shell nanocrystals. The PIA-MAA-QDs were characterized by TEM, DLS, PL and UV-vis measurements, further studies are carried out to determine the chemical, thermal and photochemical stability of the water-soluble QDs.In Chapter 3, the amphiphilic copolymer, poly (stearyl methacrylate-co- methylacrylic acid) (PSM) was synthesized using solution copolymerization. PSMs with different hydrophobic ratio were synthesized by controlling monomer molar ratio, and the PSMs with appropriate molecular weight were determined, which could be used to coat QDs. Base on the investigation of hydrophobic ratios of PSMs, PSM/QDs mass/volume ratios and reaction time, a simple but effective phase transfer method is developed to make the CdSe/ZnS QDs water-soluble completely. We characterize the optical properties and sizes of our QDs samples using multiple tools, we also examine the stability against chemical, photochemical, and thermal treatments of these QDs. In Chapter 4, the amphiphilic comb coplymers, poly (stearyl methacrylate-co- methylacrylic acid)-ethanolamine (PSM-EtA) and poly (stearyl methacrylate-co- methylacrylic acid)-polyethylene glycol amine (PSM-PEG), were synthesized by amidation reaction using EtA and amino- polyethylene glycol 2000 (NH2PEG2000). Next, FA was embedded by PSM-EtA to prepare PSM-EtA@FA drug loading. The maximum drug loading of the vehicle was 520 mg/g, and the embedding ratio was 90%. Adriamycin hydrochloride (DOX) was embedded by PSM-PEG to prepare PSM-PEG@DOX drug loading. The maximum drug loading of the vehicle was 460 mg/g, and the embedding ratio was 80%. The delivery properties of the two vehicles were detected with different pH and tempature conditions. The results showed that PSM-EtA and PSM-PEG were favourable drug carriers to realize sustained release, which could be applied in biomedicine.In Chapter 5, the amphiphilic comb targeting coplymers, poly (stearyl methacrylate-co- methylacrylic acid)-polyethylene glycol amine-urokinase (PSM- PEG-uk), were synthesized by amidation reaction. Next, water soluble PSM-PEG- uk@IO and PSM-PEG-uk@IO-DOX nanoparticles were prepared using PSM-PEG and PSM-PEG-uk as phase transfer agents. The diameter distribution, paramagnetism and embedding ratio were studied. The two nanoparticles were uniform and kept the similar superparamagnetism as the original IO nanoparticles. The maximum drug loading of PSM-PEG-uk@IO-DOX was 200 mg/g, and the embedding ratio was 80%. Furthermore, four fluorescent nanoparticles were prepared, that is, PSM-PEG@QDs, PSM-PEG-uk1@QDs, PSM-PEG-uk2@QDs and PSM-PEG-uk2@QDs-DOX. The four nanoparticles were uniform and kept the similar optical properties as the original QDs. The maximum drug loading of PSM-PEG-uk@QDs-DOX was 210 mg/g, and the embedding ratio was 83%. The nanoparticle drug loading vehicle was hoped to be applied in biomedicine field.