Bacterial isolation by lectin-modified microengines.

New template-based self-propelled gold/nickel/polyaniline/platinum (Au/Ni/PANI/Pt) microtubular engines, functionalized with the Concanavalin A (ConA) lectin bioreceptor, are shown to be extremely useful for the rapid, real-time isolation of Escherichia coli (E. coli) bacteria from fuel-enhanced environmental, food, and clinical samples. These multifunctional microtube engines combine the selective capture of E. coli with the uptake of polymeric drug-carrier particles to provide an attractive motion-based theranostics strategy. Triggered release of the captured bacteria is demonstrated by movement through a low-pH glycine-based dissociation solution. The smaller size of the new polymer-metal microengines offers convenient, direct, and label-free optical visualization of the captured bacteria and discrimination against nontarget cells.

Cargo-towing fuel-free magnetic nanoswimmers for targeted drug delivery.

Fuel-free nanomotors are essential for future in-vivo biomedical transport and drug-delivery applications. Herein, the first example of directed delivery of drug-loaded magnetic polymeric particles using magnetically driven flexible nanoswimmers is described. It is demonstrated that flexible magnetic nickel-silver nanoswimmers (5-6 µm in length and 200 nm in diameter) are able to transport micrometer particles at high speeds of more than 10 µm s(-1) (more than 0.2 body lengths per revolution in dimensionless speed). The fundamental mechanism of the cargo-towing ability of these magnetic (fuel-free) nanowire motors is modelled, and the hydrodynamic features of these cargo-loaded motors discussed. The effect of the cargo size on swimming performance is evaluated experimentally and compared to a theoretical model, emphasizing the interplay between hydrodynamic drag forces and boundary actuation. The latter leads to an unusual increase of the propulsion speed at an intermediate particle size. Potential applications of these cargo-towing nanoswimmers are demonstrated by using the directed delivery of drug-loaded microparticles to HeLa cancer cells in biological media. Transport of the drug carriers through a microchannel from the pick-up zone to the release microwell is further illustrated. It is expected that magnetically driven nanoswimmers will provide a new approach for the rapid delivery of target-specific drug carriers to predetermined destinations.

Functionalized micromachines for selective and rapid isolation of nucleic acid targets from complex samples.

The transport properties of single-strand DNA probe-modified self-propelling micromachines are exploited for "on-the-fly" hybridization and selective single-step isolation of target nucleic acids from "raw" microliter biological samples (serum, urine, crude E. coli lysate, saliva). The rapid movement of the guided modified microrockets induces fluid convection, which enhances the hybridization efficiency, thus enabling the rapid and selective isolation of nucleic acid targets from untreated samples. The integration of these autonomous microrockets into a lab-on-chip device that provides both nucleic acid isolation and downstream analysis could thus be attractive for diverse applications.

Dynamic isolation and unloading of target proteins by aptamer-modified microtransporters.

We describe here a new strategy for isolating target proteins from complex biological samples based on an aptamer-modified self-propelled microtube engine. For this purpose, a thiolated thrombin or a mixed thrombin-ATP aptamer (prehybridized with a thiolated short DNA) was coassembled with mercaptohexanol onto the gold surface of these microtube engines. The rapid movement of the aptamer-modified microtransporter resulted in highly selective and rapid capture of the target thrombin, with an effective discrimination against a large excess of nontarget proteins. Release of the captured thrombin can be triggered by the addition of ATP that can bind and displace the immobilized mixed thrombin-ATP aptamer in 20 min. The rapid loading and unloading abilities demonstrated by these selective microtransporters are illustrated in complex matrixes such as human serum and plasma. The new motion-driven protein isolation platform represents a new approach in bioanalytical chemistry based on active transport of proteins and offers considerable promise for diverse diagnostic applications.

Mndal, a new interferon-inducible family member, is highly polymorphic, suppresses cell growth, and may modify plasmacytoma susceptibility.

The human HIN-200 gene cluster and its mouse counterpart, the interferon inducible-200 (Ifi200) family, both on Chr 1, are associated with several diseases, including solid tumors and lupus. Our study was initiated to identify the modifier gene(s) encoded by the Pctm locus, in which mouse B-cell plasmacytomas induced by pristane are associated with heterozygosity of Chr 1 genes near the Ifi200 cluster. A screen for differentially expressed genes in granulomatous tissues induced by pristane in resistant and susceptible strains identified a new Ifi200 member whose expression was 1000-fold higher in the strain carrying the resistant allele of Pctm and was the most highly expressed Ifi200 gene. The gene, designated Mndal (for MNDA-like, myeloid nuclear differentiation antigen-like), was absent in the susceptible genome, as were genomic sequences upstream of Ifi203, the gene adjacent to Mndal. Ectopic expression of MNDAL suppressed cell growth, which, together with the disease susceptibility of heterozygotes at the Pctm locus, suggests that Mndal, perhaps with Ifi203, acts as a tumor suppressor and display(s) haploinsufficiency. Mndal is highly polymorphic among inbred mouse strains, because it is absent in 10 of 24 strains. This polymorphism may have implications for other disease modifiers mapping to the same region.

Rapid delivery of drug carriers propelled and navigated by catalytic nanoshuttles.

This paper reports the first proof-of-concept of using catalytic nanoshuttles to pick up, transport, and release common drug carriers including biocompatible and biodegradable polymeric particles and liposomes. The rapid transport of a wide size range of drug-loaded particles (100 nm-3.0 µm) with a speed approximately three orders of magnitude faster than that of the particles transported by Brownian motion demonstrates the high propulsion power of the nanoshuttles. The nanoshuttles' navigation ability is illustrated by the transport of the drug carriers through a microchannel from the pick-up to the release microwell. Such ability of nanomotors to rapidly deliver drug-loaded polymeric particles and liposomes to their target destination represents a novel approach towards transporting drug carriers in a target-specific manner. This also potentially addresses the obstacles of current nanoparticle drug delivery, such as off-targeting of particles. While an initial concept of actively transporting therapeutic particles is demonstrated in vitro in this paper, future efforts will focus on practical in vivo motor-based targeted drug delivery in connection to fuel-free nanovehicles.

Chemical sensing based on catalytic nanomotors: motion-based detection of trace silver.

A motion-based chemical sensing involving fuel-driven nanomotors is demonstrated. The new protocol relies on the use of an optical microscope for tracking changes in the speed of nanowire motors in the presence of the target analyte. Selective and sensitive measurements of trace silver ions are illustrated based on the dramatic and specific acceleration of bimetal nanowire motors in the presence of silver. Such nanomotor-based measurements would lead to a wide range of novel and powerful chemical and biological sensing protocols.

Thermal modulation of nanomotor movement.

Motion control is essential for various applications of man-made nanomachines. The ability to control and regulate the movement of catalytic nanowire motors is illustrated by applying short heat pulses that allow the motors to be accelerated or slowed down. The accelerated motion observed during the heat pulses is attributed primarily to the thermal activation of the redox reactions of the H(2)O(2) fuel at the Pt and Au segments and to the decreased viscosity of the aqueous medium at elevated temperatures. The thermally modulated motion during repetitive temperature on/off cycles is highly reversible and fast, with speeds of 14 and 45 microm s(-1) at 25 and 65 degrees C, respectively. A wide range of speeds can be generated by tailoring the temperature to yield a linear speed-temperature dependence. Through the use of nickel-containing nanomotors, the ability to combine the thermally regulated motion of catalytic nanomotors with magnetic guidance is also demonstrated. Such on-demand control of the movement of nanowire motors holds great promise for complex operations of future manmade nanomachines and for creating more sophisticated nanomotors.

A Study on the Bioavailability of a Proprietary, Sustained-release Formulation of Astaxanthin.

CONTEXT: Astaxanthin has been shown to provide important health benefits, such as functioning as an anti-inflammatory, antioxidant, anticancer, and cardioprotective agent. Astaxanthin is a lipid-soluble molecule with low oral bioavailability, which limits its therapeutic potential. The low oral bioavailability is due to dissolution limitations in the gastrointestinal fluids. OBJECTIVE: The objective of this study was to compare the relative bioavailability of a proprietary sustained-release formulation of astaxanthin (astaxanthin-SR)-a micronized dispersion of astaxanthin oil that is 2.5% astaxanthin in a sustained-release matrix-with that of an unformulated astaxanthin oil containing 10% astaxanthin. DESIGN: A dissolution study compared the solubility of formulated and unformulated astaxanthin oils. The research team also performed a single-dose, 24-h crossover, uptake study. SETTING: The dissolution study took place at BioActives (Worcester, MA, USA). The single-dose study was done at the MAZE Laboratories (Purchase, NY, USA). PARTICIPANTS: Six healthy male and female volunteers aged 21 to 66 y took part in the single-dose study. The participants were people from the community. INTERVENTION: That proprietary formulation is a free-flowing paste that is able to form a stable dispersion in water and achieve sustained-release when presented in a capsule form. For the samples used in the dissolution study, hard gelatin capsules were filled either with the unformulated astaxanthin oil or with the proprietary astaxanthin-SR formulation, both with the equivalent of 10 mg of astaxanthin. For the single-dose study, participants received a 60-mg dose of astaxanthin in each form, as capsules, with a 15-d washout period between the 2 doses. The astaxanthin-SR capsules were administered after breakfast, and blood samples were drawn at 3, 8, 10, and 24 h postintervention. After a 15-d washout period, the protocol was repeated with astaxanthin oil capsules. OUTCOME MEASURES: For the dissolution study, the astaxanthin was quantified using spectrophotometry. For the single-dose study, plasma astaxanthin was quantified using reverse-phase high-performance liquid chromatography equipped with an ultraviolet-visible detector and a Phenomenex Synergy Hydro-RP column 150 × 4.6 mm, 4 µm (Phenomenex, Torrance, CA, USA) at room temperature. RESULTS: The dissolution study indicated that the astaxanthin-SR formulation formed a stable dispersion in the simulated gastric and intestinal fluids. The formulation also showed greater dissolution for 12 h at all points tested, compared with the astaxanthin oil, which showed no dissolution during the same period of 12 h. The results of the single-dose uptake study indicated that the astaxanthin-SR formulation was 3.6 times more bioavailable than astaxanthin oil, with P < .0005 in a paired t test. In addition, all participants showed uptake from the sustained-release formulation. CONCLUSIONS: The formulation of astaxanthin oil in a sustained-release matrix significantly improved the absorption of astaxanthin. The formulation also reduced interindividual variations in absorption. Participants who were poor absorbers from the unformulated astaxanthin oil, showed higher absorption with the astaxanthin-SR formulation.

Bioavailability of a Sustained Release Formulation of Curcumin.

CONTEXT: Curcumin has a number of beneficial effects, such as functioning as a potent antioxidant,1 anti-inflammatory, 2 and anticancer agent. Because of its poor oral bioavailability, very high oral doses and repeated dosing have been used to obtain effective plasma levels, with mixed results. High doses of curcumin may cause gastric disturbance, often resulting in poor patient compliance. OBJECTIVE: The objective of this study was to compare the relative bioavailability of MicroActive Curcumin-an advanced, micronized formulation of curcumin that is 25% curcuminoids in a sustained release matrix-with that of an unformulated, 95% pure curcumin powder. DESIGN: A dissolution study compared the solubility of the formulated and the unformulated curcumin. The research team also performed a single-dose, 12-h, crossover uptake study with 10 participants and a high-dose tolerability and accumulation study with 3 participants, comparing the 2 forms of curcumin. SETTING: The study was done in MAZE Laboratories (Purchase, NY, USA). PARTICIPANTS: Ten healthy male and female volunteers, aged 21-66 y, took part in the single-dose study. Three participants, 2 female and 1 male aged 40-55 y, took part in the tolerability and accumulation study. The participants were people from the community. INTERVENTION: For the dissolution study, the research team filled hard gelatin capsules with unformulated 95% curcumin powder and the MicroActive Curcumin powder to the equivalent of 25 mg curcuminoids. For the single-dose study, participants received 500 mg of curcumin in 2 forms. MicroActive Curcumin capsules were administered after breakfast, and blood samples were drawn at 1, 2, 4, 8, and 12 h postdose. After a 7-d washout period, the protocol was repeated for unformulated, 95% curcumin powder capsules. For the tolerability study, the unformulated, 95% curcumin powder was given at a dose that provided 2 g of curcumin for 7 d followed by 5 g of curcumin for an additional 7 d. After a washout period of 14 d, the protocol was repeated with MicroActive Curcumin. Participants then continued to take the MicroActive Curcumin for >3 mo. OUTCOME MEASURES: For the dissolution study, the curcumin was quantified at room temperature using reverse-phase, high-performance liquid chromatography (HPLC) with a Phenomenex Luna column (150 × 4.6 mm, 5 µm) (Phenomenex Inc, Torrance, CA, USA). For the single-dose and the tolerability studies, hydrolysis of conjugates and extraction of curcuminoids from the plasma were performed. The curcuminoids were quantified using reverse-phase HPLC with an ultraviolet-visible detector as described above. RESULTS: The dissolution study indicated that the sustained-release curcumin had greater dissolution for 12 h at all points tested, compared with the unformulated curcumin. Very little of the unformulated curcumin powder had been released at the end of the 12 h. The results of the single-dose uptake study indicated that the sustained-release formula was 9.7 × more bioavailable than the unformulated powder (P < .001, paired t test). Additionally, all participants showed uptake from the sustained-release formulation. That formulation also resulted in significant increases in the plasma demethoxylated curcuminoids, but the research team did not observe the same increases for the unformulated curcumin powder. The sustained-release formulation was well tolerated, without adverse effects in the high-dose tolerability study. CONCLUSIONS: Formulation of micronized curcumin in a combination of surfactants, oils, and polymers improves the absorption of curcumin. In addition, the unique plasma demethylated curcuminoid profile may enhance the therapeutic effects of MicroActive Curcumin not observed with unformulated curcumin at moderate and well-tolerated doses. MicroActive Curcumin was well tolerated, without any adverse effects in a high-dose tolerability study. These properties have the potential to make high-dose curcumin supplementation more accessible through simplified incorporation into food and beverage preparations.

Motion-based DNA detection using catalytic nanomotors.

Synthetic nanomotors, which convert chemical energy into autonomous motion, hold considerable promise for diverse applications. In this paper, we show the use of synthetic nanomotors for detecting DNA and bacterial ribosomal RNA in a fast, simple and sensitive manner. The new motion-driven DNA-sensing concept relies on measuring changes in the speed of unmodified catalytic nanomotors induced by the dissolution of silver nanoparticle tags captured in a sandwich DNA hybridization assay. The concentration-dependent distance signals are visualized using optical microscopy, particularly through straight-line traces by magnetically aligned 'racing' nanomotors. This nanomotor biodetection strategy could be extended to monitor a wide range of biomolecular interactions using different motion transduction schemes, thus providing a versatile and powerful tool for detecting biological targets.

Template-assisted fabrication of salt-independent catalytic tubular microengines.

A simplified template-assisted layering approach for preparing catalytic conical tube microjet engines based on sequential deposition of platinum and gold on an etched silver wire template followed by dicing and dissolution of the template is described. The method allows detailed control over the tube parameters and hence upon the performance of the microengine. The recoiling bubble propulsion mechanism of the tubular microengine, associated with the ejection of internally generated oxygen microbubbles, addresses the ionic-strength limitation of catalytic nanowire motors and leads to a salt-independent movement. Similar rates of bubble generation and motor speeds are observed in salt-free and salt-rich media (at elevated ionic-strength environments as high as 1 M NaCl). Plating of an intermediate nickel layer facilitates a magnetically guided motion as well as the pickup and transport of large (magnetic) "cargo". Surfactant addition is shown to decrease the surface tension and offer a more frequent formation of dense smaller bubbles. The new and improved motor capabilities along with the simple preparation route hold great promise for using catalytic micromotors in diverse and important applications.

Electrochemically-triggered motion of catalytic nanomotors.

An electrochemically-controlled movement of catalytic nanomotors, including a cyclic 'on/off' activation of the nanomotor motion and a fine speed control, is illustrated.