Synthesis and applications of functional polymer nanoparticles

• Main Authors: LEE, SHIH-HUI, 李世惠
• Other Authors: Doong, Ruey-an
• Format: Others
• Language: en_US
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/10328720725253236576

博士 === 國立清華大學 === 生醫工程與環境科學系 === 101 === The nano-sized materials have recently received much attention due to the unique physical and chemical properties which are different from bulk materials. Polymer nanoparticles can be designed for many purposes, such as removal of pollutants/contaminants, drug delivery, imaging, diagnostics, isolation, and purification) provides opportunities for transformative approaches to separations, therapeutics, diagnostics and biomacromolecule isolation. This is a vibrant area of research with recent successes including specific adsorbent, therapeutic reagents, drug delivery vehicles, sensors, toxin neutralization and enzyme inhibition. The main purpose of this study was to fabricate various types of polymer nanoparticles with various functionalities to capture targets from small molecules to macromolecules. For targeting small molecules including acetaminophen and estradiol, molecularly imprinted polymer (MIP) nanoparticles were synthesized by precipitation polymerization. Template (acetaminophen) and functional monomer (methacrylic acid, MAA) were mixed with various porogens (chloroform, toluene and acetonitrile) to form the complex by hydrogen binding and hydrophobic interaction. In addition, trimethylpropane trimethacrylate (TRIM) and 2, 2´-azobis- isobutyronitrile (AIBN) were used as the cross-linker and the initiator, respectively. Acetonitrile was used as porogen to obtain spherical MIPs with high surface area of 447.2 m2/g. The particle size of MIPs increased from 177 nm to 2472 nm by simply tuning the ratio of TRIM to MAA from 0.43 to 8.64. Imprinting factor was obtained up to 2.4 when the ratio of the acetaminophen to MAA was 3.0. The maximum adsorption amount of acetaminophen on the MIPs, by fitting Langmuir equation, was calculated to be 0.35 mg/g and the adsorption constant was 0.045 L/mg. In contrast, the maximum adsorption amount and adsorption constant of the NIP synthesized in acetonitrile were 0.22 mg/g and 0.021 L/mg, respectively. The MIPs can capture acetaminophen rapidly and reach saturation within the first 30 min. In addition, the MIPs have good selectivity towards acetaminophen adsorption and shows low capacity to estradiol and aspirin, which clearly indicates that the method developed, can be used to fabricate MIPs with high affinity and selectivity. MIP nanoparticles can overcome the problem of low mass transfer, but it is hard to recover or separate from aqueous solutions except high speed centrifugation. Core-shell materials, the highly functional materials with modified properties, have recently attracted considerable attention. The method was established to fabricate Fe3O4/SiO2@MIP nanoparticles with high affinity to the target which can be easily recovered by an external magnetic field. Magnetic nanoparticles were prepared by co-precipitation method and then Stöber method was utilized to fabricate Fe3O4/SiO2 nanoparticles. The results of scanning electron microscopy (SEM), transmission electron microscopy (TEM), and fourier transform infrared spectroscopy (FTIR) showed that Fe3O4/SiO2@MIP core-shell nanoparticles can be successfully fabricated by the method developed in this study. The maximum capacities of Fe3O4/SiO2@MIPs are 0.24 and 1.08 mg/g for acetaminophen and estradiol, respectively. In addition, most of the Fe3O4/SiO2@MIP nanoparticles can be recovered from the solution by an external magnetic field. The method established is facile and promising to prepare Fe3O4/SiO2@MIP nanocomposites as the candidates for the removal of acetaminophen and estradiol in the environment and wastewater. Biomolcule imprinting has many challenges, such as the denaturalization of biolmolecules during the polymerization, the difficulty of the removal template and the slow mass transfer due to the large size and so on. Therefore, we developed the polymer nanoparticle library used to screen the interaction between nanoparticles and biomolecules to substitute imprinting method. The protein target of this study is the 150 kDa protein immunoglobulin G (IgG), the workhorse protein for research, diagnostics and, increasingly, therapeutic applications. Dynamic light scattering (DLS) and quartz crystal microbalance (QCM) were used to identify synthetic polymer NPs (50~65 nm) composed of 40% TBAm, 20% AAc, 2% Bis and 38% NIPAm that bonded to the Fc fragment of IgG. The affinity and amount of nanoparticles bound to IgG was pH dependent. The hydrogel nanoparticles inhibited protein A binding to the Fc domain at pH 5.5, but not at pH 7.3. A computational analysis was used to identify potential NP-protein interaction sites. Candidates included a nanoparticle binding domain that overlapped with the protein A–Fc binding domain at pH 5.5. The computational analysis supported the inhibition experimental results and was attributed to the difference in the charged state of histidine residues. Affinity of the nanoparticles (3.5~8.5 nM) to the Fc domain at pH 5.5 is comparable to protein A at pH 7. Due to pH-dependent binding, facile procedures to capture and release IgG were developed. These results suggest that synthetic polymer nanoparticles can be engineered to have an intrinsic affinity to a specific domain of a large biomacromolecule. In addition, the nanoparticles we synthesized have high potential to replace protein A for the protein purification. Results obtained in this study clearly demonstrated that the functional nanoparticles can be facilely designed for capturing the molecules from small molecules to biomolecules by precipitation polymerization. The nanoparticles synthesized by the methods we established are excellent candidates to be applied in many fields such as in environmental and biomedical application.