Jingjing Nie

One-Pot Preparation of Hollow Silica Spheres by Using Thermosensitive Poly(N-isopropylacrylamide) as a Reversible Template

Hollow silica nanospheres with mesoporous shells were successfully fabricated with a new one-pot strategy by using a thermosensitive polymer, poly(N-isopropylacrylamide) (PNIPAm), as a reversible template without the need of further calcination or chemical etching. By simply regulating the solution temperature with respect to the lower critical solution temperature (LCST) of PNIPAm, PNIPAm chains can reversibly form aggregates or dissolve in aqueous solution. The thermosensitive character makes PNIPAm chains behave as soft templates for the formation of core-shell silica nanospheres at elevated temperature (>LCST), and they will then diffuse out of the cores at lower temperature (<LCST), leading to the formation of hollow silica nanospheres. The TEM, SEM, XRD, and N(2) adsorption-desorption results indicate that the shells of such hollow silica nanospheres also contain large quantities of irregular mesopores. This new strategy was also tested with another thermosensitive polymer, poly(vinyl methyl ether) (PVME). However, only solid silica nanospheres with a broad size distribution were obtained when PVME was used. We speculated on the possible formation mechanism of hollow silica nanospheres with PNIPAm templates. The effects of the initial concentration of PNIPAm, the molecular weight of PNIPAm, and the pretreatment of silica precursor on the morphology and size of the resultant hollow silica nanospheres were also investigated. The PNIPAm soft templates were confirmed to be recyclable.

Preparation and Properties of Thermo-sensitive Organic/Inorganic Hybrid Microgels

By utilizing the hydrolysis and condensation of the methoxysilyl groups, thermo-sensitive organic/inorganic hybrid poly[ N-isopropylacrylamide- co-3-(trimethoxysilyl)propylmethacrylate] [P(NIPAm- co-TMSPMA)] microgels were successfully prepared via two different methods without addition of any surfactant. First, the microgels were obtained by a two-step method; that is, the linear copolymer P(NIPAm- co-TMSPMA) was first synthesized by free radical copolymerization, and the aqueous solution of the copolymer was then heated above its low critical solution temperature (LCST) to give colloid particles, which were subsequently cross-linked via the hydrolysis and condensation of the methoxysilyl groups to form the microgels. Second, the microgels were also prepared via conventional surfactant-free emulsion polymerization (SFEP) of the monomers NIPAm and TMSPMA. TMSPMA can act as the cross-linkable monomer. No surfactant was involved in the preparation of the hybrid microgels. The obtained microgels were rather spherical and exhibited reversible thermo-sensitive behavior. The size, morphology, swellability, and phase transition behavior of the microgels were dependent on the initial copolymer or monomer concentration, preparation temperature, and the content of TMSPMA. The size of microgels obtained by SFEP was found to be more uniform than that by the two-step method. The hybrid microgels obtained by these two methods had more homogeneous microstructures than those prepared via conventional emulsion polymerization with chemical cross-linker N, N-methylene-bisacrylamide.

Thermosensitive Ionic Microgels via Surfactant-Free Emulsion Copolymerization and in Situ Quaternization Cross-Linking

A type of thermosensitive ionic microgel was successfully prepared via the simultaneous quaternized cross-linking reaction during the surfactant-free emulsion copolymerization of N-isopropylacrylamide (NIPAm) as the main monomer and 1-vinylimidazole or 4-vinylpyridine as the comonomer. 1,4-Dibromobutane and 1,6-dibromohexane were used as the halogenated compounds to quaternize the tertiary amine in the comonomer, leading to the formation of a cross-linking network and thermosensitive ionic microgels. The sizes, morphologies, and properties of the obtained ionic microgels were systematically investigated by using transmission electron microscopy (TEM), dynamic and static light scattering (DLS and SLS), electrophoretic light scattering (ELS), thermogravimetric analyses (TGA), and UV-visible spectroscopy. The obtained ionic microgels were spherical in shape with narrow size distribution. These ionic microgels exhibited thermosensitive behavior and a unique feature of poly(ionic liquid) in aqueous solutions, of which the counteranions of the microgels could be changed by anion exchange reaction with BF4K or lithium trifluoromethyl sulfonate (PFM-Li). After the anion exchange reaction, the ionic microgels were stable in aqueous solution and could be well dispersed in the solvents with different polarities, depending on the type of counteranion. The sizes and thermosensitive behavior of the ionic microgels could be well tuned by controlling the quaternization extent, the type of comonomer, halogenated compounds, and counteranions. The ionic microgels showed superior swelling properties in aqueous solution. Furthermore, these ionic microgels also showed capabilities to encapsulate and release the anionic dyes, like methyl orange, in aqueous solutions.

Poly(N-vinylpyrrolidinone) Microgels: Preparation, Biocompatibility, and Potential Application as Drug Carriers

The biocompatible poly(N-vinylpyrrolidinone) (PNVP) microgels were synthesized via surfactant free emulsion polymerization with N-vinylpyrrolidinone (NVP) as the monomer and ethylene glycol dimethacrylate (EGDMA) as the cross-linker at 60 °C. The obtained PNVP microgels are spherical in shape with hydrodynamic diameter of approximately 200 nm and narrow size distribution. The PNVP microgels show rough surfaces due to the different reaction rates of monomer NVP and cross-linker EGDMA. The obtained PNVP microgels could well disperse in phosphate-buffered saline (PBS) solution with long-term stability, which make them candidates for bioapplications. The results of 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) tests indicated that the PNVP microgels are biocompatible with low toxicity even at a concentration of 1000 μg/mL. By labeling the PNVP microgels with fluorescein comonomer, it was demonstrated that the PNVP microgels could be uptaken by human embryonic kidney 293 (HEK-293) cells. The experimental results indicated that the release of isoniazid (INH, the hydrophilic model drug) could be well described by a Fickian release, whereas the microgels exhibited burst release for 5-fluorouracil (5-fu, the hydrophobic model drug).

4-(2-Pyridylazo)-resorcinol Functionalized Thermosensitive Ionic Microgels for Optical Detection of Heavy Metal Ions at Nanomolar Level

4-(2-Pyridylazo)-resorcinol (PAR) functionalized thermosensitive ionic microgels (PAR-MG) were synthesized by a one-pot quaternization method. The PAR-MG microgels were spherical in shape with radius of ca. 166.0 nm and narrow size distribution and exhibited thermo-sensitivity in aqueous solution. The PAR-MG microgels could optically detect trace heavy metal ions, such as Cu(2+), Mn(2+), Pb(2+), Zn(2+), and Ni(2+), in aqueous solutions with high selectivity and sensitivity. The PAR-MG microgel suspensions exhibited characteristic color with the presence of various trace heavy metal ions, which could be visually distinguished by naked eyes. The limit of colorimetric detection (DL) was determined to be 38 nM for Cu(2+) at pH 3, 12 nM for Cu(2+) at pH 7, and 14, 79, 20, and 21 nM for Mn(2+), Pb(2+), Zn(2+), and Ni(2+), respectively, at pH 11, which was lower than (or close to) the United States Environmental Protection Agency standard for the safety limit of these heavy metal ions in drinking water. The mechanism of detection was attributed to the chelation between the nitrogen atoms and o-hydroxyl groups of PAR within the microgels and heavy metal ions.

Functionalized Ionic Microgel Sensor Array for Colorimetric Detection and Discrimination of Metal Ions

A functional ionic microgel sensor array was developed by using 1-(2-pyridinylazo)-2-naphthaleno (PAN)- and bromothymol blue (BTB)-functionalized ionic microgels, which were designed and synthesized by quaternization reaction and anion-exchange reaction, respectively. The PAN microgels (PAN-MG) and BTB microgels (BTB-MG) were spherical in shape with a narrow size distribution and exhibited characteristic colors in aqueous solution in the presence of various trace-metal ions, which could be visually distinguished by the naked eye. Such microgels could be used for the colorimetric detection of various metal ions in aqueous solution at submicromolar levels, which were lower than the U.S. Environmental Protection Agency standard for the safety limit of metal ions in drinking water. A total of 10 species of metal ions in aqueous solution, Ba2+, Cr3+, Mn2+, Pb2+, Fe3+, Co2+, Zn2+, Ni2+, Cu2+, and Al3+, were successfully discriminated by the as-constructed microgel sensor array combined with discriminant analysis, agglomerative hierarchical clustering, and leave-one-out cross-validation analysis.

Thermo-sensitive Poly(DEGMMA-co-MEA) Microgels: Synthesis, Characterization and Interfacial Interaction with Adsorbed Protein Layer *

The novel microgels, poly[di(ethylene glycol) methyl ether methacrylate-co-2-methoxyethyl acrylate] poly(DEGMMA-co-MEA) microgels, were synthesized. The poly(DEGMMA-co-MEA) microgels were thermo-sensitive and exhibited a volume phase transitive temperature (VPTT) of 14–22 °C. The incorporation of hydrophobic comonomer MEA shifted the VPTT of poly(DEGMMA-co-MEA) microgels to lower temperatures. The interfacial interaction of poly(DEGMMA-co-MEA) microgels and three model proteins, namely fibrinogen, bovine serum albumin and lysozyme, was investigated by quartz crystal microbalance (QCM). An injection sequence of “microgel-after-protein” was then established for the real-time study of the interaction of proteins and the microgels at their swollen and collapsed states by using QCM technique. The results indicated that the interfacial interaction of poly(DEGMMA-co-MEA) microgels and adsorbed protein layers was mainly determined by the electrostatic interaction. Because poly(DEGMMA-co-MEA) microgels were negatively charged in Tris-HCl buffer solution (pH = 7.4), the microgels did not adsorb on negatively charged fibrinogen and bovine serum albumin layers but strongly adsorbed on positively charged lysozyme layer. Stronger interaction between lysozyme and the microgels at collapsed state (i.e. at 37 °C) was observed. Furthermore, the incorporation of MEA might weaken the interaction between poly(DEGMMA-co-MEA) microgels and proteins.

Thermo-sensitive ionic microgels via post quaternization cross-linking: fabrication, property, and potential application

A post quaternized cross-linking strategy was reported to fabricate thermo-sensitive ionic microgels from thermo-sensitive linear copolymer poly(N-isopropylacrylamide-co-1-vinylimidazole) [P(NIPAm-co-VIM)] or poly(N-isopropylacrylamide-co-4-vinylpyridine) [P(NIPAm-co-4VP)] in aqueous solution at elevated temperature above its critical transition temperature (Tc). 1,4-dibromobutane, 1,5-dibromopentane, or 1,6-dibromohexane were chosen as the quaternization cross-linker to quaternize the imidazole or pyridine moieties, leading to the formation of cross-linking and ionic network. Transmission electron microscopy (TEM), dynamic and static light scattering (DLS & SLS), electrophoretic light scattering (ELS), and UV-visible spectroscopy were used to systematically investigate the sizes, morphologies, and properties of the obtained microgels. The sizes, swelling properties, and uniformity of microgels could be tuned by selecting proper quaternization cross-linking reaction temperature and cross-linkers. The obtained ionic microgels showed capability to adsorb the heavy metal salts like K2Cr2O7 in aqueous solution via the anion exchange reactions. It was also demonstrated that other functional groups could be introduced into the microgel networks if the unquaternized moieties were available.

Thermo-sensitive poly(VCL-4VP-NVP) ionic microgels: synthesis, cytotoxicity, hemocompatibility, and sustained release of anti-inflammatory drugs

Thermosensitive poly(VCL-4VP-NVP) ionic microgels were prepared by in situ quaternization crosslinking reaction during surfactant free emulsion polymerization (SFEP) with N-vinylcaprolactam (VCL) as the main monomer, 4-vinylpyridine (4VP) as the quaternizable co-monomer, N-vinyl-2-pyrrolidone (NVP) as the second co-monomer and 1,6-dibromohexane (6Br) as the quaternization crosslinker. The obtained ionic microgels were spherical in shape with a narrow size distribution and exhibited thermo-sensitive behavior. These ionic microgels showed low cytotoxicity at concentrations lower than 25 µg mL−1, excellent hemocompatibility at concentrations up to 1000 µg mL−1, and could be up taken into the cytoplasm regime of HEK-293 cells without entering the nucleus. It was found that these ionic microgels were suitable for the loading and sustained release of a nonsteroidal anti-inflammatory drug, diclofenac sodium (DS). The drug loading content (DLC) of DS in the microgels could reach ca. 12% with an encapsulation efficiency (EE) of up to 68%. Furthermore, 60% loaded DS could be sustainably released at 37 °C from the drug-loaded microgels within 400 min following a first-order exponential kinetics.

Tuning the morphology, network structure, and degradation of thermo-sensitive microgels by controlled addition of degradable cross-linker

Thermo-sensitive degradable poly(N-isopropylacrylamide) (PNIPAm)-based microgels were prepared by surfactant-free emulsion polymerization with a redox initiator pair of potassium persulfate (KPS) and N,N,N′,N′-tetramethylethylenediamine at 50xa0°C. NIPAm, sodium 2-acrylamido-2-methyl-1-propanesulfonate (AMPS-Na), and N,N′-bis(acryloyl)cystamine (BAC) were used as main monomer, anionic comonomer, and degradable cross-linker, respectively. It was found that the morphology and network structure of the resultant microgels could be tuned via the controlled addition of BAC and AMPS-Na, which, in turn, strongly affected the corresponding thermo-sensitivity, stability, and degradation behavior of the microgels. The inhomogeneous network structures of the microgels could be improved by increasing the time period tBAC between KPS initiation and the addition of BAC. The morphology of microgels changed from spherical into hollow interior spherical morphology. The stability of the microgels in physiological condition could be enhanced by the controlled addition of comonomer AMPS-Na. The extent of microgel degradation increased with increasing tBAC.