Phase Transitions of Naphthalene-2,3-carbonitride Steered by Solvent Effects and Metal Ion Concentration Variation.

The delicate regulation of structural phase transition can provide advanced approaches for fabricating desired and well-organized nanoarchitectures on surfaces. Introduction of metal ions into pure organic systems can facilitate the phase transition from hydrogen-bonded structures to metal-organic structures by coordinating with organic molecules. However, it remains a challenge to attain a phase transition dominated by variable metal coordination configurations through adjustment of the metal ion concentration. Herein, we report the phase transitions of naphthalene-2,3-carbonitride (2,3-DCN) molecules on highly oriented pyrolytic graphite (HOPG) under varying solvents and Cu2+ ion concentrations. By integrating data from scanning tunneling microscopy imaging and density functional theory calculations, it is demonstrated that phase transitions of 2,3-DCN occur through forming diverse coordination configurations where Cu2+ ions can coordinate with 2,3-DCN and 1-nonanoic acid or Cl- ions to form different ligand components with a coordination number of 4 when varying the molar ratios of 2,3-DCN to Cu2+ ion in the 1-nonanoic acid solvent. However, in the case of 1-heptanoic acid as a solvent, the self-assembly structure of 2,3-DCN only changes via the alteration of hydrogen bonding sites and Cu2+ ions do not coordinate with 2,3-DCN molecules. These findings provide valuable insights into the coordination behavior of metal ions in different solvents.

Quantitative proteomic analysis of glycosylated proteins enriched from urine samples with magnetic ConA nanoparticles identifies potential biomarkers for small cell lung cancer.

Lung cancer has high morbidity and mortality and small cell lung cancer (SCLC) is a highly invasive malignant tumor with a very unfavorable survival rate. Early diagnosis and treatment can result in better prognosis for the SCLC patients but current diagnostic methods are either invasive or incapable for large-scale screen. Therefore, discovering biomarkers for early diagnosis of SCLC is of importance. In this work, we covalently coupled Concanavalin A (ConA) to functionalized magnetic nanoparticles to obtain magnetic ConA-nanoparticles (ConA-NPs) for the enrichment of glycosylated proteins. We then purified glycosylated proteins in 36 urine samples from 9 healthy controls, 9 SCLC patients, 9 lung adenocarcinoma (LUAD) patients, and 9 lung squamous cell carcinoma (LUSC) patients. The purified glycosylated proteins were digested and analyzed by LC-MS/MS for identification and quantification. Among the 398 identified proteins, 20, 15, and 1 glycosylated protein(s), respectively, were upregulated in the urine of SCLC, LUAD, and LUSC patients. Immunoblotting experiments further demonstrated that cathepsin C and transferrin were significantly upregulated in the ConA-NP purified urine of SCLC patients. This work suggests that glycosylated cathepsin C and transferrin might be able to serve as potential biomarkers for the noninvasive diagnosis of SCLC patients.

Biocompatible Injectable Magnetic Hydrogel Formed by Dynamic Coordination Network.

Magnetic hydrogel that can respond to a magnetic stimulus is a promising biomaterial for tissue regeneration and cancer treatment. In this study, a novel magnetic hydrogel is formed by simply mixing bisphosphonate (BP)-modified hyaluronic acid (i.e., HA-BP) polymeric solution and iron oxide (Fe3O4) nanoparticle dispersion, in which the hydrogel networks are cross-linked by BP groups and iron atoms on the surface of particle. The iron-BP coordination chemistry affords a dynamic network, characterized by self-healing, shear-thinning, and smoothly injectable properties. Moreover, the HA-BP·Fe3O4 magnetic hydrogel demonstrates heat-generation characterization under an alternating magnetic field. The animal experiments confirm the biocompatibilities of HA-BP·Fe3O4 hydrogel, which presents the hydrogels potential for tissue regeneration and anticancer treatment applications.

A novel phase function describing light scattering of layers containing colloidal nanospheres.

Light scattering from small particles exhibit unique angular scattering distributions, which are strongly dependent on the radius to wavelength ratio as well as the refractive index contrast between the particles and the surrounding medium. As the concentration of the particles increases, multiple scattering becomes important. This complicates the description of the angular scattering patterns, and in many cases one has to resort to empirical phase functions. We have measured the angle dependence of light scattering from a polymer layer containing sub-micron metallic and dielectric particles. The samples exhibited strongly forward and backward peaked scattering patterns, which were fitted to a number of empirical approximative phase functions. We found that a novel two-term Reynolds-McCormick (TTRM) phase function gave the best fit to the experimental data in all cases. The feasibility of the TTRM approach was further validated by good agreement with numerical simulations of Mie single scattering phase functions at various wavelengths and sizes, ranging from the Rayleigh scattering regime to the geometrical optics regime. Hence, the widely adaptable TTRM approach is able to describe angular scattering distributions of different kinds of nanospheres and nanocomposites, both in the single scattering and multiple scattering regimes.

Feasibility of using DNA-immobilized nanocellulose-based immunoadsorbent for systemic lupus erythematosus plasmapheresis.

The goal of this project was to study the feasibility of using a DNA-immobilized nanocellulose-based immunoadsorbent for possible application in medical apheresis such as systemic lupus erythematosus (SLE) treatment. Calf thymus DNA was bound to high surface area nanocellulose membrane at varying concentrations using UV-irradiation. The DNA-immobilized samples were characterized with scanning electron microscopy, atomic force microscopy, and phosphorus elemental analysis. The anti-ds-DNA IgG binding was tested in vitro using ELISA. The produced sample showed high affinity in vitro to bind anti-ds-DNA-antibodies from mice, as much as 80% of added IgG was bound by the membrane. Furthermore, the binding efficiency was quantitatively dependent on the amount of immobilized DNA onto nanocellulose membrane. The described nanocellulose membranes are interesting immunoadsorbents for continued clinical studies.

Covalent immobilization of molecularly imprinted polymer nanoparticles on a gold surface using carbodiimide coupling for chemical sensing.

One challenging task in building (bio)chemical sensors is the efficient and stable immobilization of receptor on a suitable transducer. Herein, we report a method for covalent immobilization of molecularly imprinted core-shell nanoparticles for construction of robust chemical sensors. The imprinted nanoparticles with a core-shell structure have selective molecular binding sites in the core and multiple amino groups in the shell. The model Au transducer surface is first functionalized with a self-assembled monolayer of 11-mercaptoundecanoic acid. The 11-mercaptoundecanoic acid is activated by treatment with carbodiimide/N-hydroxysuccinimide and then reacted with the core-shell nanoparticles to form amide bonds. We have characterized the process by studying the treated surfaces after each preparation step using atomic force microscopy, scanning electron microscopy, fluorescence microscopy, contact angle measurements and X-ray photoelectron spectroscopy. The microscopy results show the successful immobilization of the imprinted nanoparticles on the surface. The photoelectron spectroscopy results further confirm the success of each functionalization step. Further, the amino groups on the MIP surface were activated by electrostatically adsorbing negatively charged Au colloids. The functionalized surface was shown to be active for surface enhanced Raman scattering detection of propranolol. The particle immobilization and surface enhanced Raman scattering approach described here has a general applicability for constructing chemical sensors in different formats.

Photoconjugation of Molecularly Imprinted Polymer Nanoparticles for Surface-Enhanced Raman Detection of Propranolol.

We report a simple and versatile method to covalently immobilize molecularly imprinted polymer (MIP) nanoparticles on a Raman active substrate (Klarite) using a disulfide-derivatized perfluorophenylazide (PFPA-disulfide). Gold-coated Klarite was functionalized with PFPA-disulfide via a gold-sulfur bond. Upon light radiation, the available azido groups were converted to highly reactive singlet perfluorophenyl nitrene that undergoes a CH insertion reaction and form covalent bonds with the MIP nanoparticles. The resulting surfaces were characterized using scanning electron microscopy and surface enhanced Raman spectroscopy to study the morphology and template affinity of the surfaces, respectively. The Raman measurements clearly show a dose-responsive signal when propranolol binds to the MIP surface. Because the MIP particles were covalently attached to the Raman active substrate, the sensing surface was stable and could be reused after regeneration in acetic acid solution. The MIP-based Raman sensor was used successfully to detect propranolol in urine samples (7.7 × 10(-4) M). Our results show that the high selectivity of MIPs and the fingerprint Raman identification can be integrated into a compact sensing unit using high-efficiency photoconjugation. Thus, the method proposed is reliable, efficient and fast for fabricating label-free chemical sensors.

Covalent immobilization of molecularly imprinted polymer nanoparticles using an epoxy silane.

Molecularly imprinted polymers (MIPs) can be used as antibody mimics to develop robust chemical sensors. One challenging problem in using MIPs for sensor development is the lack of reliable conjugation chemistry that allows MIPs to be fixed on transducer surface. In this work, we study the use of epoxy silane to immobilize MIP nanoparticles on model transducer surfaces without impairing the function of the immobilized nanoparticles. The MIP nanoparticles with a core-shell structure have selective molecular binding sites in the core and multiple amino groups in the shell. The model transducer surface is functionalized with a self-assembled monolayer of epoxy silane, which reacts with the core-shell MIP particles to enable straightforward immobilization. The whole process is characterized by studying the treated surfaces after each preparation step using atomic force microscopy, scanning electron microscopy, fluorescence microscopy, contact angle measurements and X-ray photoelectron spectroscopy. The microscopy results show that the MIP particles are immobilized uniformly on surface. The photoelectron spectroscopy results further confirm the action of each functionalization step. The molecular selectivity of the MIP-functionalized surface is verified by radioligand binding analysis. The particle immobilization approach described here has a general applicability for constructing selective chemical sensors in different formats.

Photoconjugation of molecularly imprinted polymer with magnetic nanoparticles.

Because of their synthetic accessibility, molecularly imprinted polymer (MIP) nanoparticles are ideal building blocks for preparing multifunctional composites. In this work, we developed a general photocoupling chemistry to enable simple conjugation of MIP nanoparticles with inorganic magnetic nanoparticles. We first synthesized MIP nanoparticles using propranolol as a model template and perfluorophenyl azide-modified silica-coated magnetic nanoparticles. Using a simple photoactivation followed by facile purification with a magnet, we obtained magnetic composite particles that showed selective uptake of propranolol. We characterized the nanoparticles and composite materials using FT-IR, TEM, fluorescence spectroscopy, and radioligand binding analysis. Through the high molecular selectivity of the magnetic composite, we demonstrated the nondestructive feature and the high efficiency of the photocoupling chemistry. The versatile photoconjugation method developed in this work should also be very useful for combining organic MIPs with other inorganic nanoparticles to enable new chemical sensors and high efficiency photocatalysts.

Cryogelation of molecularly imprinted nanoparticles: a macroporous structure as affinity chromatography column for removal of ß-blockers from complex samples.

In this work, a new macroporous molecularly imprinted cryogel (MIP composite cryogel) was synthesized by glutaraldehyde cross-linking reaction of poly(vinyl alcohol) (PVA) particles and amino-modified molecularly imprinted core-shell nanoparticles. The MIP core-shell nanoparticles were prepared using propranolol as a template by one-pot precipitation polymerization with sequential monomer addition. The characteristics of the MIP composite cryogel were studied by scanning electron microscopy (SEM) and texture analyzer. The macroporous structure of the composite (with the pore size varying from a few micrometers to 100 µm) enabled high mass transfer of particulate-containing fluids. In a solid phase extraction (SPE) process, the efficiency and selectivity of the MIP composite cryogel were investigated, where the cryogel was used as an affinity matrix to remove propranolol from aqueous solution as well as from complex plasma sample without prior protein precipitation. The MIP composite cryogel maintained high selectivity and stability and could be used repeatedly after regeneration.

Molecular recognition with colloidosomes enabled by imprinted polymer nanoparticles and fluorogenic boronic acid.

Multifunctional colloidosomes are prepared from molecularly imprinted polymer nanoparticles and fluorogenic boronic acid using a Cu(i)-catalyzed click reaction. The molecular selectivity of the colloidosomes was investigated by radioligand binding analysis, which indicated that the inter-particle click reaction did not affect the molecular specificity of the MIP nanoparticles on the colloidosomes for the model template, propranolol. Besides specific molecular recognition of the MIP nanoparticles, the colloidosomes also displayed dose-dependent fluorescence response to fructose at physiological pH. Moreover, the immobilized boronic acid in the core could effectively bind isoproterenol, a template analogue containing a catecholamine moiety. The depletion of isoproterenol from solution allowed the MIP nanoparticles on the colloidosomes to bind propranolol more efficiently. The pre-designed molecular selectivity and fluorescence response of the colloidosomes are interesting for potential applications in controlled delivery, chemical sensing and bioseparation.

Clickable molecularly imprinted nanoparticles.

Terminal alkynyl and azide groups are introduced on the surface of molecularly imprinted core-shell nanoparticles using precipitation polymerization. These clickable groups enable simple nanoparticle conjugation and surface modification under mild reaction conditions, opening new opportunities for nanoparticle-based assays and chemical sensing.