An Eco-Friendly Manner to Prepare Superwetting Melamine Sponges with Switchable Wettability for the Separation of Oil/Water Mixtures and Emulsions.

Oil/water separation processes have garnered significant global attention due to the quick growth in industrial development, recurring chemical leakages, and oil spills. Hence, there is a significant demand for the development of inexpensive superwetting materials in an eco-friendly manner to separate oil/water mixtures and emulsions. In this study, a superwetting melamine sponge (SMS) with switchable wettabilities was prepared by modifying melamine sponge (MS) with sodium dodecanoate. The as-prepared SMS exhibited superhydrophobicity, superoleophilicity, underwater superoleophobicity, and underoil superhydrophobicity. The SMS can be utilized in treating both light and heavy oil/water mixtures through the prewetting process. It demonstrated fast permeation fluxes (reaching 108,600 L m-2 h-1 for a light oil/water mixture and 147,700 L m-2 h-1 for a heavy oil/water mixture) and exhibited good separation efficiency (exceeding 99.56%). The compressed SMS was employed in separating surfactant-stabilized water-in-oil emulsions (SWOEs), as well as surfactant-stabilized oil-in-water emulsions (SOWEs), giving high permeation fluxes (reaching 7210 and 5054 L m-2 h-1, respectively). The oil purity for SWOEs' filtrates surpassed 99.98 wt% and the separation efficiencies of SOWEs exceeded 98.84%. Owing to their remarkable capability for separating oil/water mixtures and emulsions, eco-friendly fabrication method, and feasibility for large-scale production, our SMS has a promising potential for practical applications.

Hydrogen-bonded cytosine-endowed supramolecular polymeric nanogels: Highly efficient cancer cell targeting and enhanced therapeutic efficacy.

We demonstrate that cytosine moieties within physically cross-linked supramolecular polymers not only manipulate drug delivery and release, but also confer specific targeting of cancer cells to effectively enhance the safety and efficacy of chemotherapy-and thus hold significant potential as a new perspective for development of drug delivery systems. Herein, we successfully developed physically cross-linked supramolecular polymers (PECH-PEG-Cy) comprised of hydrogen-bonding cytosine pendant groups, hydrophilic poly(ethylene glycol) side chains, and a hydrophobic poly(epichlorohydrin) main chain. The polymers spontaneously self-assemble into a reversibly hydrogen-bonded network structure induced by cytosine and directly form spherical nanogels in aqueous solution. Nanogels with a high hydrogen-bond network density (i.e., a higher content of cytosine moieties) exhibit outstanding long-term structural stability in cell culture substrates containing serum, whereas nanogels with a relatively low hydrogen-bond network density cannot preserve their structural integrity. The nanogels also exhibit numerous unique physicochemical characteristics in aqueous solution, such as a desirable spherical size, high biocompatibility with normal and cancer cells, excellent drug encapsulation capacity, and controlled pH-responsive drug release properties. More importantly, in vitro experiments conclusively indicate the drug-loaded PECH-PEG-Cy nanogels can selectively induce cancer cell-specific apoptosis and cell death via cytosine receptor-mediated endocytosis, without significantly harming normal cells. In contrast, control drug-loaded PECH-PEG nanogels, which lack cytosine moieties in their structure, can only induce cell death in cancer cells through non-specific pathways, which significantly inhibits the induction of apoptosis. This work clearly demonstrates that the cytosine moieties in PECH-PEG-Cy nanogels confer selective affinity for the surface of cancer cells, which enhances their targeted cellular uptake, cytotoxicity, and subsequent induction of programmed cell death in cancer cells.

Ultrafast absorption mechanism of oil-emulsified micelles onto ferrous absorbents with dielectrophoresis force in the presence of polarization.

Absorption and desorption rates were generally dependent on the concentration gradient from bulk to absorbents. A novel methodology based on a capacitor with an alternating electric field (AEF) is developed to accelerate the absorption and desorption rates with the frequency manipulation. Ferrous polystyrene microspheres (PISMs) are synthesized as absorbents, which could enhance the complex permittivities as well as dielectric properties. Theoretically, the attractive force and viscous force predominately determine the particle and micelles movement in the medium under an AEF. Oil-emulsified micelles (OEM) with various viscosities were selected as absorbates. Both the OEM and microspherical absorbents assembled through the external attractive force in the presence of the AEF. When the attractive force is equal to viscous force in the medium at the characteristic frequency, the optimal absorption rate could be obtained. The absorption rate constants of pseudo-first-order for OEMs under the polarization at 50 V and 120 kHz of frequency are ca. 10 times higher than that in absence of the polarization. The desorption rate as well as recycling efficiency could be also improved at 800 kHz. The ferrous PISMs with high complex permittivity prevented the damage from the AEF, which could be recycled 10 times of absorption and desorption with frequency manipulation under the AEF. Our methodology provides novel insights for ultrafast wastewater treatment.

A CO2-Responsive Imidazole-Functionalized Fluorescent Material Mediates Cancer Chemotherapy.

We present a breakthrough in the synthesis and development of functional gas-responsive materials as highly potent anticancer agents suitable for applications in cancer treatment. Herein, we successfully synthesised a stimuli-responsive multifunctional material (I-R6G) consisting of a carbon dioxide (CO2)-sensitive imidazole moiety and spirolactam-containing conjugated rhodamine 6G (R6G) molecule. The resulting I-R6G is highly hydrophobic and non- or weakly fluorescent. Simple CO2 bubbling treatment induces hydrophobic I-R6G to completely dissolve in water and subsequently form self-assembled nanoparticles, which exhibit unique optical absorption and fluorescence behaviours in water and extremely low haemolytic ability against sheep red blood cells. Reversibility testing indicated that I-R6G undergoes reversible CO2/nitrogen (N2)-dependent stimulation in water, as its structural and physical properties can be reversibly and stably switched by alternating cycles of CO2 and N2 bubbling. Importantly, in vitro cellular assays clearly demonstrated that the CO2-protonated imidazole moiety promotes rapid internalisation of CO2-treated I-R6G into cancer cells, which subsequently induces massive levels of necrotic cell death. In contrast, CO2-treated I-R6G was not internalised and did not affect the viability of normal cells. Therefore, this newly created system may provide an innovative and efficient route to remarkably improve the selectivity, safety and efficacy of cancer treatment.

Performance Enhancement of Electrochemiluminescence with the Immunosensor Controlled Using Magnetized Masks for the Determination of Epithelial Cancer Biomarker EpCAM.

The performance of an electrochemiluminescence (ECL) immunosensor was improved with a particle gradient. SiO2-coated magnetic beads were adopted as nanocarriers for gradient manipulation and immobilized with the primary antibody. Cadmium telluride quantum dots were coated with a layer of protein G for conjugation and orientation of the secondary antibody as signal labels. ECL immunosensor gradients on the electrode were formed by magnetolithography (ML) with magnetized nickel masks of column and stripe arrays. The immunosensor generally aggregated as an island on the substrate, leading to a decrease of efficiency in the characteristic signals. Stripe arrays of magnetized nickel were designed to generate cylindrical magnetic flux on the substrate to improve the particle manipulation with the gradient. Various gradients of the sandwich-structured immunosensor substantially affected the electrochemical performance. Compared to the gradient-free immunosensor, the gradient of the immunosensor generated by ML using a 3 µm stripe array mask enhanced the ECL intensity ∼2.2 times. The results of quantification of epithelial cell adhesion molecules (EpCAM) with the gradient immunosensor showed a broad linear range (15-420 pg mL-1), a low limit of detection (5.5 pg mL-1), and high reliability for EpCAM-spiked serum samples, indicating that the immunosensor gradient substantially enhances the performance of the ECL assay.

LSPR Sensing of Epithelial Cell Adhesion Molecules through Sphere and Cavity Plasmons of a Composite Ring Array of Poly[2-(dimethylamino)ethyl methacrylate]/Gold Nanoparticles.

Self-organization facilitates the formation of specific structures as a result of constituent interactions. In this study, the bottom of a 600 nm hole array photoresist template, which was deposited with a hydrophobic atom transfer radical polymerization (ATRP) initiator, was wetted by treatment with oxygen plasma. After the removal of the photoresist template, ring patterns of the ATRP initiator were formed at the interface between the hydrophobic and wetting regions. Poly[2-(dimethylamino)ethyl methacrylate] (PDMAEMA) was grafted from the ring array of the initiator to immobilize gold nanoparticles (AuNPs) as a uniform ring array on a silicon substrate via repeated swelling/shrinking cycles. The localized surface plasmon resonance (LSPR) peak of the PDMAEMA-AuNP hybrid ring (PAHR) red-shifted after 12 swelling/shrinking cycles. In comparison to gold nanoparticles, scalable gold nanorings can effectively develop a variety of nanostructures to design LSPR-based sensors and optimize the sensing accuracy and stability. To detect epithelial cell adhesion molecules (EpCAM) during the structural change from a ring to a disk, antiEpCAM was anchored onto the PAHR as a biosensor during swelling/shrinking. The coupling of antiEpCAM and EpCAM led to asymptotical convergence from rings to disks as well as blue shifts of the LSPR peaks. Linear correlation between the blue shift and EpCAM concentration showed a limit of detection of ∼27 pg mL-1 and a linear range of 25-200 pg mL-1 for the detection of EpCAM within 30 min. The simple method of combining lithography and plasma technology provides a versatile platform for developing the scalable ring structure of AuNPs for highly sensitive and selective biosensing.

Hydrogen Bond Strength-Mediated Self-Assembly of Supramolecular Nanogels for Selective and Effective Cancer Treatment.

This study provides a significant contribution to the development of multiple hydrogen-bonded supramolecular nanocarrier systems by demonstrating that controlling the hydrogen bond strength within supramolecular polymers represents a crucial factor to tailor the drug delivery performance and enhance the effectiveness of cancer therapy. Herein, we successfully developed two kinds of poly(ethylene glycol)-based telechelic polymers Cy-PEG and UrCy-PEG having self-constituted double and quadruple hydrogen-bonding cytosine (Cy) and ureido-cytosine (UrCy) end-capped groups, respectively, which directly assemble into spherical nanogels with a number of interesting physical characteristics in aqueous solutions. The UrCy-PEG nanogels containing quadruple hydrogen-bonded UrCy dimers exhibited excellent long-term structural stability in a serum-containing biological medium, whereas the double hydrogen-bonded Cy moieties could not maintain the structural integrity of the Cy-PEG nanogels. More importantly, after the drug encapsulation process, a series of in vitro experiments clearly confirmed that drug-loaded UrCy-PEG nanogels induced selective apoptotic cell death in cancer cells without causing significant cytotoxicity to healthy cells, while drug-loaded Cy-PEG nanogels exerted nonselective cytotoxicity toward both cancer and normal cells, indicating that increasing the strength of hydrogen bonds in nanogels plays a key role in enhancing the selective cellular uptake and cytotoxicity of drugs and the subsequent induction of apoptosis in cancer cells.

An aniline trimer-based multifunctional sensor for colorimetric Fe3+, Cu2+ and Ag+ detection, and its complex for fluorescent sensing of L-tryptophan.

The detection of metal ions and amino acids by the aniline oligomer-based receptor has not been reported yet, to the best of our knowledge. In this study, an efficient multifunctional cation-amino acid sensor (CAS) with aniline moiety and chiral thiourea binding site was synthesized by the reaction of aniline trimer and (S)-(+)-1-phenyl ethyl isothiocyanate. CAS can sense Fe3+, Cu2+, Ag+ ions, and L-tryptophan. These results can be recognized by the naked eye. The appropriate pH range for the quantitative analysis of Fe3+, Cu2+, and Ag+ by CAS in DMSO/water (30 vol% water) was evaluated. The interaction between CCS and metal ions was analyzed by 1H NMR titration. The detection limits of CAS for the Cu2+, Ag+, and Fe3+ were 0.214, 0.099, and 0.147 µM, respectively. Moreover, the CASCu2+ complex can act as a turn-on fluorescence sensor for L-tryptophan. On the contrary, there is no response upon the addition of other amino acids, such as L-histidine, L-proline, L-phenylalanine, L-threonine, L-methionine, L-tyrosine, and L-cystine to CASCu2+ complex.

Preparations of Tough and Conductive PAMPS/PAA Double Network Hydrogels Containing Cellulose Nanofibers and Polypyrroles.

To afford an intact double network (sample abbr.: DN) hydrogel, two-step crosslinking reactions of poly(2-acrylamido-2-methylpropanesulfonic acid) (i.e., PAMPS first network) and then poly(acrylic acid) (i.e., PAA second network) were conducted both in the presence of crosslinker (N,N'-methylenebisacrylamide (MBAA)). Similar to the two-step processes, different contents of 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) oxidized cellulose nanofibers (TOCN: 1, 2, and 3 wt.%) were initially dispersed in the first network solutions and then crosslinked. The TOCN-containing PAMPS first networks subsequently soaked in AA and crosslinker and conducted the second network crosslinking reactions (TOCN was then abbreviated as T for DN samples). As the third step, various (T-)DN hydrogels were then treated with different concentrations of FeCl3(aq) solutions (5, 50, 100, and 200 mM). Through incorporations of ferric ions into (T-)DN hydrogels, notably, three purposes are targeted: (i) strengthen the (T-)DN hydrogels through ionic bonding, (ii) significantly render ionic conductivity of hydrogels, and (iii) serve as a catalyst for the forth step to proceed with in situ chemical oxidative polymerizations of pyrroles to afford polypyrrole-containing (sample abbr.: Py) hydrogels [i.e., (T-)Py-DN samples]. The characteristic functional groups of PAMPS, PAA, and Py were confirmed by FT-IR. Uniform microstructures were observed by cryo scanning electron microscopy (cryo-SEM). These results indicated that homogeneous composites of T-Py-DN hydrogels were obtained through the four-step process. All dry samples showed similar thermal degradation behaviors from the thermogravimetric analysis (TGA). The T2-Py5-DN sample (i.e., containing 2 wt.% TOCN with 5 mM FeCl3(aq) treatment) showed the best tensile strength and strain at breaking properties (i.e., σTb = 450 kPa and εTb = 106%). With the same compositions, a high conductivity of 3.34 × 10-3 S/cm was acquired. The tough T2-Py5-DN hydrogel displayed good conductive reversibility during several "stretching-and-releasing" cycles of 50-100-0%, demonstrating a promising candidate for bioelectronic or biomaterial applications.

CO2-Responsive Water-Soluble Conjugated Polymers for In Vitro and In Vivo Biological Imaging.

Water-soluble conjugated polymers (WCPs) composed of a hydrophobic polythiophene main chain with hydrophilic tertiary amine side-chains can directly self-assemble into sphere-like nano-objects in an aqueous solution due to phase separation between the hydrophilic and hydrophobic segments of the polymeric structure. Due to the presence of gas-responsive tertiary amine moieties in the spherical structure, the resulting polymers rapidly and reversibly tune their structural features, surface charge, and fluorescence performance in response to alternating carbon dioxide (CO2) and nitrogen (N2) bubbling, which leads to significantly enhanced fluorescence and surface charge switching properties and a stable cycle of on and off switching response. In vitro studies confirmed that the CO2-treated polymers exhibited extremely low cytotoxicity and enhanced cellular uptake ability in normal and tumor cells, and thus possess significantly improved fluorescence stability, distribution, and endocytic uptake efficiency within cellular organisms compared to the pristine polymer. More importantly, in vivo assays demonstrated that the CO2-treated polymers displayed excellent biocompatibility and high fluorescence enhancement in living zebrafish, whereas the fluorescence intensity and stability of zebrafish incubated with the pristine polymer decreased linearly over time. Thus, these CO2 and N2-responsive WCPs could potentially be applied as multifunctional fluorescent probes for in vivo biological imaging.

A Dynamic Hanging-Drop System for Mesenchymal Stem Cell Culture.

There have been many microfluid technologies combined with hanging-drop for cell culture gotten developed in the past decade. A common problem within these devices is that the cell suspension introduced at the central inlet could cause a number of cells in each microwell to not regularize. Also, the instability of droplets during the spheroid formation remains an unsolved ordeal. In this study, we designed a microfluidic-based hanging-drop culture system with the design of taper-tube that can increase the stability of droplets while enhancing the rate of liquid exchange. A ring is surrounding the taper-tube. The ring can hold the cells to enable us to seed an adequate amount of cells before perfusion. Moreover, during the period of cell culture, the mechanical force around the cell is relatively low to prevent stem cells from differentiate and maintain the phenotype. As a result of our hanging system design, cells are designed to accumulate at the bottom of the droplet. This method enhances convenience for observation activities and analysis of experiments. Thus, this microfluid chip can be used as an in vitro platform representing in vivo physiological conditions, and can be useful in regenerative therapy.

Biodegradable Redox-Sensitive Star Polymer Nanomicelles for Enhancing Doxorubicin Delivery.

A typical amphiphilic star polymer adamantane-[poly(lactic-co-glycolic acid)-bis(2-carboxyethyl) sulfide-poly(ethylene glycol) monomethyl ether)]4 with a specific hydrophilic/redox-sensitive/hydrophobic structure was designed and synthesized through ring opening and esterification reactions. The self-assembled nanomicelles were used as doxorubicin (DOX) delivery vehicles with suitable critical micelle concentrations (5.0 mg/L). After the drug being loaded, drug-loaded micelles showed good drug-loading efficiency (10.39%), encapsulation efficiency (58.1%), and drug release (up to 60%) under simulated biological environment conditions. In addition, the backbone structure of the biodegradable polymer was easily hydrolyzed by the action of biological enzymes. As expected, cell-based studies showed that the designed polymer micelles possessed good biocompatibility (a survival rate of 85% for NH-3T3 cells). Moreover, the drug (DOX) still maintained good anti-cancer effects after being loaded, which caused 40% of MCF-7 cells to survive. These redox-sensitive micelles showed anti-tumor therapeutic potential.

Self-Assembled pH-Responsive Polymeric Micelles for Highly Efficient, Noncytotoxic Delivery of Doxorubicin Chemotherapy To Inhibit Macrophage Activation: In Vitro Investigation.

Self-assembled pH-responsive polymeric micelles, a combination of hydrophilic poly(ethylene glycol) segments and hydrogen bonding interactions within a biocompatible polyurethane substrate, can spontaneously self-assemble into highly controlled, nanosized micelles in aqueous solution. These newly developed micelles exhibit excellent pH-responsive behavior and biocompatibility, highly controlled drug (doxorubicin; DOX) release behavior, and high drug encapsulation stability in different aqueous environments, making the micelles highly attractive potential candidates for safer, more effective drug delivery in applications such as cancer chemotherapy. In addition, in vitro cell studies revealed the drug-loaded micelles possessed excellent drug entrapment stability and low cytotoxicity toward macrophages under normal physiological conditions (pH 7.4, 37 °C). When the pH of the culture media was reduced to 6.0 to mimic the acidic tumor microenvironment, the drug-loaded micelles triggered rapid release of DOX within the cells, which induced potent antiproliferative and cytotoxic effects in vitro. Importantly, fluorescent imaging and flow cytometric analyses confirmed the DOX-loaded micelles were efficiently delivered into the cytoplasm of the cells via endocytosis and then subsequently gradually translocated into the nucleus. Therefore, these multifunctional micelles could serve as delivery vehicles for precise, effective, controlled drug release to prevent accumulation and activation of tumor-promoting tumor-associated macrophages in cancer tissues. Thus, this unique system may offer a potential route toward the practical realization of next-generation pH-responsive therapeutic delivery systems.

Binary-blend fibber-based capture assay of circulating tumor cells for clinical diagnosis of colorectal cancer.

BACKGROUND: In addition to conventional approaches, detecting and characterizing CTCs in patient blood allows for early diagnosis of cancer metastasis. METHODS: We blended poly(ethylene oxide) (PEO) into nylon-6 through electrospinning to generate a fibrous matbased circulating tumour cells (CTCs) assay. The contents of nylon-6 and PEO in the electrospun blend fibrous mats (EBFMs) were optimized to facilitate high cell-substrate affinity and low leukocyte adsorption. RESULTS: Compared with the IsoFlux System, a commercial instrument for CTC detection, the CTC assay of EBFMs exhibited lower false positive readings and high sensitivity and selectivity with preclinical specimens. Furthermore, we examined the clinical diagnosis accuracy of colorectal cancer, using the CTC assay and compared the results with those identified through pathological analyses of biopsies from colonoscopies. Our positive expressions of colorectal cancer through CTC detection completely matched those recognized through the pathological analyses for the individuals having stage II, III, and IV colorectal cancer. Nevertheless, two in four individuals having stage I colorectal cancer, recognized through pathological analysis of biopsies from colonoscopies, exhibited positive expression of CTCs. Ten individuals were identified through pathological analysis as having no colorectal tumours. Nevertheless, two of these ten individuals exhibited positive expression of CTCs. CONCLUSIONS: Thus, in this population, the low cost EBFMs exhibited considerable capture efficiency for the non-invasive diagnosis of colorectal cancer.

pH-Sensitive Micelles Based on Star Copolymer Ad-(PCL-b-PDEAEMA-b-PPEGMA)4 for Controlled Drug Delivery.

Enhancing drug loading efficacy and stability of polymeric micelles remains a grand challenge. Here we develop adamantane-based star copolymers adamantane-[poly(ε-caprolactone)-b-poly(2-(diethylamino)ethyl methacrylate)-b-poly(poly(ethylene glycol) methyl ether methacrylate)]4 (Ad-(PCL-b-PDEAEMA-b-PPEGMA)4) and their self-assembled micelles for controlled drug delivery. Results show that the polymers have excellent stability in solution with low critical micelle concentration (CMC) (0.0025⁻0.0034 mg/mL) and the apparent base dissociation constant (pKb) of the polymers is from 5.31 to 6.05. Dynamic light scattering analysis exhibits the great environmental response capability of the pH-sensitive micelles according to particle sizes and zeta potentials. With the synergy effect of the adamantane and hydrophobic block, the micelles display the high Doxorubicin (DOX) loading efficacy (up to 22.4%). The DOX release study shows that the micelles are capable of controlled release for drug. This work indicates the Ad-(PCL-b-PDEAEMA-b-PPEGMA)4 micelles may provide new guidelines for drug control and release system in overcoming cancer treatment.

Self-assembled supramolecular polymers with tailorable properties that enhance cell attachment and proliferation.

Self-assembled supramolecular scaffolds, a combination of noncovalent interactions within a biocompatible polymer substrate, can be used for efficient construction of highly-controlled self-organizing hierarchical structures; these newly-developed biomaterials exhibit excellent mechanical properties, tunable surface hydrophilicity, low cytotoxicity and high biodegradability, making them highly attractive for tissue engineering and regenerative medicine applications. Herein, we demonstrate a novel supramolecular poly(ε-caprolactone) (PCL) containing self-complementary sextuple hydrogen-bonded uracil-diamidopyridine (U-DPy) moieties, which undergoes spontaneous self-assembly to form supramolecular polymer networks. Inclusion of various U-DPy contents enhanced the mechanical strength and viscosities of the resulting materials by up to two orders of magnitude compared to control PCL. Surface wettability and morphological studies confirmed physically-crosslinked films can be readily tailored to provide the desired surface properties. Cell viability assays indicated the excellent in vitro biocompatibility of U-DPy-functionalized substrates and indicate the potential of these materials for various biomedical applications. More importantly, mouse fibroblast NIH/3T3 cells cultured on these substrates displayed a more elongated cell morphology and had substantially higher cell densities than cells seeded on control PCL substrate, which indicates that introduction of U-DPy moieties into polymer matrixes could be used to create tissue culture surfaces that enhance cell attachment and proliferation. This new system is suggested as a potential route towards the practical realization of next-generation tissue-engineering scaffolds. STATEMENT OF SIGNIFICANCE: In this study, we report a significant breakthrough in development of self-assembled supramolecular polymers to form well-defined scaffolds through self-complementary hydrogen-bonding interactions. These newly developed materials exhibited extremely good mechanical properties, fine-tunable hydrophilic characteristics and excellent biocompatibility due to hydrogen-bond-induced physical cross-linking. Importantly, cell adhesion and proliferation assays indicated that these substrates efficiently promoted the growth of mouse embryonic fibroblasts NIH/3T3 cells in vitro. Thus, this finding provides a simple and effective route for the development of next-generation tissue-engineering scaffolds that have improved mechanical properties, increased surface hydrophilicity and can enhance the growth and biological activity of adherent cells.

Rapid fabrication of carbon quantum dots as multifunctional nanovehicles for dual-modal targeted imaging and chemotherapy.

Herein, we synthesized an S, N, and Gd tri-element doped magnetofluorescent carbon quantum dots (GdNS@CQDs) within 10min by using a one-pot microwave method. Our results showed that these magnetofluorescent GdNS@CQDs have excellent fluorescent and magnetic properties. Moreover, GdNS@CQDs exhibited high stability at physiological conditions and ionic strength. These magnetofluorescent GdNS@CQDs were conjugated with a folic acid, denoted as FA-GdNS@CQDs, for targeting dual modal fluorescence/magnetic resonance (MR) imaging. The in vitro and in vivo studies confirmed the high biocompatibility and low toxicity of FA-GdNS@CQDs. FA-GdNS@CQDs enhanced the MR response as compared to that for commercial Gd-DTPA. The targeting capabilities of FA-GdNS@CQDs were confirmed in HeLa and HepG2 cells using in vitro fluorescence and MR dual modality imaging. Additionally, an anticancer drug, doxorubicin, was incorporated into the FA-GdNS@CQDs forming FA-GdNS@CQDs-DOX, which enables targeted drug delivery. Importantly, the prepared FA-GdNS@CQDs-DOX showed a high quantity of doxorubicin loading capacity (about 80%) and pH-sensitive drug release. The uptake into cancer cells and the intracellular location of the FA-GdNS@CQDs were observed by confocal laser scanning microscopy. We also successfully demonstrated in vivo fluorescence bio imaging of the FA-GdNS@CQDs, using zebrafish as an animal model. STATEMENT OF SIGNIFICANCE: In this manuscript, we reported a facial, rapid, and environmental friendly method to fabricate hetero atoms including gadolinium, nitrogen, and sulfur doped multi-functional magnetofluorescent carbon quantum dots (GdNS@CQDs) nanocomposite. These multifunctional GdNS@CQDs were conjugated with a folic acid for targeting dual modal fluorescence/magnetic resonance imaging. Additionally, an anticancer drug, doxorubicin, was incorporated into the nanocomposite forming FA-GdNS@CQDs-DOX, which enables targeted drug delivery. We have developed GdNS@CQDs with integrated functions for simultaneous in vitro cell imaging, targeting, and pH-sensitive controlled drug release in HeLa cells. Furthermore, we successfully demonstrated the use of this material for in vivo fluorescence imaging, using zebrafish as an animal model.

Highly efficient drug delivery systems based on functional supramolecular polymers: In vitro evaluation.

The novel concept of modifying and enhancing the properties of existing functional micelles through self-complementary interactions has significant potential. In this study, a practical approach to living polymerization of functionalized thermoresponsive monomers enabled the incorporation of self-constituted multiple hydrogen bonded groups into micelles that have potential as supramolecular drug-delivery systems. Phase transitions and morphological studies in aqueous solution showed that the microstructure can be controlled to achieve well-defined vesicle-like micelles with respect to the strength of the hydrogen bond segment. Thus, the resulting micelles have a very low critical micellization concentration and very high loading capacity (16.1%), making the loading process extremely stable and efficient. Incorporation of the anticancer drug doxorubicin (DOX) affected the micellization process in aqueous solution and enabled fine-tuning of drug loading and precise control of drug release rate with excellent sensitivity. Release studies in vitro showed that DOX-loaded micelles exerted dose-dependent cytotoxicity against human liver carcinoma (HepG2) cells at the physiological temperature of 37°C. In addition, DOX-loaded micelles were efficiently endocytosed by the cancer cells, which may enable the micelles to serve as suitable vehicles for effective delivery of anticancer drugs to primary tumors and metastatic disease. This newly developed material may provide a potential route towards next-generation drug delivery vehicles. STATEMENT OF SIGNIFICANCE: A breakthrough innovation in water-based thermo-responsive polymers has enabled significant progress in developing smart stimuli-responsive nanocarriers by generating novel "supramolecular polymeric micelles" via self-complementary hydrogen-bonding interactions. These newly developed micelles exhibit extremely high micellar stability and drug loading capacity (up to 16%), excellent thermo-responsive behavior and precise control of drug release rate due to hydrogen-bond-induced physical cross-linking. In addition, doxorubicin-loaded micelles were efficiently endocytosed by the cancer cells, which allows them to serve as suitable vehicles for effective delivery of anticancer drugs to primary tumors and metastatic disease. Thus, this work provides a potential route for the development of next generation multifunctional nanocarriers that have improved safety and to increase the therapeutic efficacy of anticancer therapy.

Clinical diagnosis of colorectal cancer using electrospun triple-blend fibrous mat-based capture assay of circulating tumor cells.

Conventional in vitro circulating tumor cell (CTC) detection methods are always limited by the blood sample volume because of the extremely low abundance of CTCs among the large number of hematologic cells. The aim of this study was to overcome this limitation by designing and constructing an in vitro CTC capture assay. We blended poly(sulfobetaine methacrylate) (PSBMA) and poly(acrylic acid) (PAA) into nylon-6 through electrospinning to generate a fibrous mat-based capture assay of CTCs. The contents of nylon-6, PSBMA, and PAA in the electrospun triple-blend fibrous mats (ETBFMs) were optimized to avoid degradation and to balance between the non-biofouling behavior and the antibody immobilizing efficiency. In addition, we examined the capture ability of CTCs for clinical diagnoses of colorectal cancer, in comparison with the results identified through pathological analyses of biopsies from colonoscopies. For nine individuals with stage II, III, and IV colorectal cancer, our CTC detection with ETBFMs provided complete positive expression. Two of four individuals were diagnosed to possess stage I colorectal cancer. Two of seven individuals without colorectal tumor, as identified through pathological analyses of biopsies, exhibited positive expression of CTCs. These positive results suggest that such ETBFMs are promising materials for in vitro CTC capture assays.

Functionalized graphene nanomaterials: new insight into direct exfoliation of graphite with supramolecular polymers.

A novel urea-cytosine end-capped polypropylene glycol (UrCy-PPG) can self-assemble into a long-range ordered lamellar microstructure on the surface of graphene, due to the strong specific interactions between UrCy-PPG and graphene. In addition, the graphene composite produced exhibits a high conductivity (∼1093 S m(-1)) with a dramatic thermo-responsive ON/OFF resistance-switching behavior (10 consecutive cycles).