Time-Delayed Anticancer Effect of an Extremely Low Frequency Alternating Magnetic Field and Multimodal Protein-Tannin-Mitoxantrone Carriers with Brillouin Microspectroscopy Visualization In Vitro.

The effect of an extremely low frequency alternating magnetic field (ELF AMF) at frequencies of 17, 48, and 95 Hz at 100 mT on free and internalized 4T1 breast cancer cell submicron magnetic mineral carriers with an anticancer drug, mitoxantrone, was shown. The alternating magnetic field (100 mT; 17, 48, 95 Hz; time of treatment-10.5 min with a 30 s delay) does not lead to the significant destruction of carrier shells and release of mitoxantrone or bovine serum albumin from them according to the data of spectrophotometry, or the heating of carriers in the process of exposure to magnetic fields. The most optimal set of factors that would lead to the suppression of proliferation and survival of cells with anticancer drug carriers on the third day (in comparison with the control and first day) is exposure to an alternating magnetic field of 100 mT in a pulsed mode with a frequency of 95 Hz. The presence of magnetic nanocarriers in cell lines was carried out by a direct label-free method, space-resolved Brillouin light scattering (BLS) spectrometry, which was realized for the first time. The analysis of the series of integrated BLS spectra showed an increase in the magnetic phase in cells with a growth in the number of particles per cell (from 10 to 100) after their internalization. The safety of magnetic carriers in the release of their constituent ions has been evaluated using atomic absorption spectrometry.

Polyurethane/n-Octadecane Phase-Change Microcapsules via Emulsion Interfacial Polymerization: The Effect of Paraffin Loading on Capsule Shell Formation and Latent Heat Storage Properties.

Organic phase-change materials (PCMs) hold promise in developing advanced thermoregulation and responsive energy systems owing to their high latent heat capacity and thermal reliability. However, organic PCMs are prone to leakages in the liquid state and, thus, are hardly applicable in their pristine form. Herein, we encapsulated organic PCM n-Octadecane into polyurethane capsules via polymerization of commercially available polymethylene polyphenylene isocyanate and polyethylene glycol at the interface oil-in-water emulsion and studied how various n-Octadecane feeding affected the shell formation, capsule structure, and latent heat storage properties. The successful shell polymerization and encapsulation of n-Octadecane dissolved in the oil core was verified by confocal microscopy and Fourier-transform infrared spectroscopy. The mean capsule size varied from 9.4 to 16.7 µm while the shell was found to reduce in thickness from 460 to 220 nm as the n-Octadecane feeding increased. Conversely, the latent heat storage capacity increased from 50 to 132 J/g corresponding to the growth in actual n-Octadecane content from 25% to 67% as revealed by differential scanning calorimetry. The actual n-Octadecane content increased non-linearly along with the n-Octadecane feeding and reached a plateau at 66-67% corresponded to 3.44-3.69 core-to-monomer ratio. Finally, the capsules with the reasonable combination of structural and thermal properties were evaluated as a thermoregulating additive to a commercially available paint.

Natural Fibrous Materials Based on Fungal Mycelium Hyphae as Porous Supports for Shape-Stable Phase-Change Composites.

Adsorption of organic phase-change materials (PCMs) by the porous matrix of microfibrillar cellulose (MFC) is a simple and versatile way to prepare shape-stable phase-change composites, which are promising as sustainable thermoregulating additives to construction materials. However, due to MFC inherent morphology, the resulting composites have relatively low poured density that complicates their introduction in sufficient amounts, for instance, into mortar mixes. Unlike MFC, fungal mycelium has, by an order, less fibrils thickness and, thus, possesses significantly higher poured density. Herein, we studied the feasibility of fungal mycelium-based matrices as alternative biopolymeric porous supports for preparation of sustainable and shape-stable phase-change composites. Two methods were employed to prepare the porous mycelium-based supports. The first one was the solid-state fermentation, which resulted in partial biotransformation of MFCs to mycelium hyphae, while the second one was the liquid-state surface fermentation, used to cultivate the reference matrix of Trametes hirsuta hyphae. The phase-change composites were prepared by adsorption of model organic PCMs on porous biopolymer matrices. The mass ratio of support/PCM was 40/60 wt%. The composites were studied with respect to their structure, composition, poured density, latent heat storage properties, and thermal and shape stability. The employment of the partially transformed to mycelium-hyphae MFC fibers was found to be a suitable way to prepare phase-change composites with improved poured density while preserving a reasonable latent heat capacity and shape stability as compared to the MFC/PCM composites.

Degradation of Hybrid Drug Delivery Carriers with a Mineral Core and a Protein-Tannin Shell under Proteolytic Hydrolases.

Hybrid carriers with the mineral CaCO3/Fe3O4 core and the protein-tannin shell are attractive for drug delivery applications due to reliable coupling of anticancer drugs with protein-tannin complex and the possibility of remote control over drug localization and delivery by the external magnetic field. This study aims to elucidate the mechanisms of drug release via enzymatic degradation of a protein-tannin carrier shell triggered by proteolytic hydrolases trypsin and pepsin under physiological conditions. To do this, the carriers were incubated with the enzyme solutions in special buffers to maintain the enzyme activity. The time-lapse spectrophotometric and electron microscopy measurements were carried out to evaluate the degradation of the carriers. It was established that the protein-tannin complex demonstrates the different degradation behavior depending on the enzyme type and buffer medium. The incubation in trypsin solution mostly resulted in the protein shell degradation. The incubation in pepsin solution did not affect the protein component; however, the citric buffer stimulates the degradation of the mineral core. The presented results allow for predicting the degradation pathways of the carriers including the release profile of the loaded cargo under physiological conditions. The viability of 4T1 breast cancer cells with mineral magnetic carriers with protein-tannin shells was investigated, and their movement in the fields of action of the permanent magnet was shown.

Key Points in Remote-Controlled Drug Delivery: From the Carrier Design to Clinical Trials.

The increased research activity aiming at improved delivery of pharmaceutical molecules indicates the expansion of the field. An efficient therapeutic delivery approach is based on the optimal choice of drug-carrying vehicle, successful targeting, and payload release enabling the site-specific accumulation of the therapeutic molecules. However, designing the formulation endowed with the targeting properties in vitro does not guarantee its selective delivery in vivo. The various biological barriers that the carrier encounters upon intravascular administration should be adequately addressed in its overall design to reduce the off-target effects and unwanted toxicity in vivo and thereby enhance the therapeutic efficacy of the payload. Here, we discuss the main parameters of remote-controlled drug delivery systems: (i) key principles of the carrier selection; (ii) the most significant physiological barriers and limitations associated with the drug delivery; (iii) major concepts for its targeting and cargo release stimulation by external stimuli in vivo. The clinical translation for drug delivery systems is also described along with the main challenges, key parameters, and examples of successfully translated drug delivery platforms. The essential steps on the way from drug delivery system design to clinical trials are summarized, arranged, and discussed.

Clay Composites for Thermal Energy Storage: A Review.

The development of novel materials and approaches for effective energy consumption and the employment of renewable energy sources is one of the current trends in modern material science. With this respect, the number of researches is focused on the effective harvesting and storage of solar energy for various applications. Phase change materials (PCMs) are known to be able to store thermal energy of the sunlight due to adsorption and release of latent heat through reversible phase transitions. Therefore, PCMs are promising as functional additives to construction materials and paints for advanced thermoregulation in building and industry. However, bare PCMs have limited practical applications. Organic PCMs like paraffins suffer from material leakage when undergoing in a liquid state while inorganic ones like salt hydrates lack long-term stability after multiple phase transitions. To avoid this, the loading of PCMs in porous matrices are intensively studied along with the thermal properties of the resulted composites. The loading of PCMs in microcontainers of natural porous or layered clay materials appears as a simple and cost-effective method of encapsulation significantly improving the shape and cyclic stability of PCMs. Additionally, the inclusion of functional clay containers into construction materials allows for improving their mechanical and flame-retardant properties. This article summarizes the recent progress in the preparation of composites based on PCM-loaded clay microcontainers along with their future perspectives as functional additives in thermo-regulating materials.

Detection of Rare Objects by Flow Cytometry: Imaging, Cell Sorting, and Deep Learning Approaches.

Flow cytometry nowadays is among the main working instruments in modern biology paving the way for clinics to provide early, quick, and reliable diagnostics of many blood-related diseases. The major problem for clinical applications is the detection of rare pathogenic objects in patient blood. These objects can be circulating tumor cells, very rare during the early stages of cancer development, various microorganisms and parasites in the blood during acute blood infections. All of these rare diagnostic objects can be detected and identified very rapidly to save a patient's life. This review outlines the main techniques of visualization of rare objects in the blood flow, methods for extraction of such objects from the blood flow for further investigations and new approaches to identify the objects automatically with the modern deep learning methods.

Freezing-Induced Loading of TiO2 into Porous Vaterite Microparticles: Preparation of CaCO3/TiO2 Composites as Templates To Assemble UV-Responsive Microcapsules for Wastewater Treatment.

The photocatalytic degradation of organic molecules is one of the effective ways for water purification. At this point, photocatalytic microreactor systems seem to be promising to enhance the versatility of the photoassisted degradation approach. Herein, we propose photoresponsive microcapsules prepared via layer-by-layer assembly of polyelectrolytes on the novel CaCO3/TiO2 composite template cores. The preparation of CaCO3/TiO2 composite particles is challenging because of the poor compatibility of TiO2 and CaCO3 in an aqueous medium. To prepare stable CaCO3/TiO2 composites, TiO2 nanoparticles were loaded into mesoporous CaCO3 microparticles with a freezing-induced loading technique. The inclusion of TiO2 nanoparticles into CaCO3 templates was evaluated with scanning electron microscopy and elemental analysis with respect to their type, concentration, and number of loading iterations. Upon polyelectrolyte shell assembly, the CaCO3 matrix was dissolved, resulting in microreactor capsules loaded with TiO2 nanoparticles. The photoresponsive properties of the resulted capsules were tested by photoinduced degradation of the low-molecule dye rhodamine B in aqueous solution and fluorescently labeled polymer molecules absorbed on the capsule surface under UV light. The exposure of the capsules to UV light resulted in a pronounced degradation of rhodamine B in capsule microvolume and fluorescent molecules on the capsule surface. Finally, the versatility of preparation of multifunctional photocatalytic and magnetically responsive capsules was demonstrated by iterative freezing-induced loading of TiO2 and magnetite Fe3O4 nanoparticles into CaCO3 templates.

Effect of Systemic Polyelectrolyte Microcapsule Administration on the Blood Flow Dynamics of Vital Organs.

Polyelectrolyte microcapsules and other targeted drug delivery systems could substantially reduce the side effects of drug and overall toxicity. At the same time, the cardiovascular system is a unique transport avenue that can deliver drug carriers to any tissue and organ. However, one of the most important potential problems of drug carrier systemic administration in clinical practice is that the carriers might cause circulatory disorders, the development of pulmonary embolism, ischemia, and tissue necrosis due to the blockage of small capillaries. Thus, the presented work aims to find out the processes occurring in the bloodstream after the systemic injection of polyelectrolyte capsules that are 5 µm in size. It was shown that 1 min after injection, the number of circulating capsules decreases several times, and after 15 min less than 1% of the injected dose is registered in the blood. By this time, most capsules accumulate in the lungs, liver, and kidneys. However, magnetic field action could slightly increase the accumulation of capsules in the region-of-interest. For the first time, we have investigated the real-time blood flow changes in vital organs in vivo after intravenous injection of microcapsules using a laser speckle contrast imaging system. We have demonstrated that the organism can adapt to the emergence of drug carriers in the blood and their accumulation in the vessels of vital organs. Additionally, we have evaluated the safety of the intravenous administration of various doses of microcapsules.

Focused ultrasound-mediated fluorescence of composite microcapsules loaded with magnetite nanoparticles: In vitro and in vivo study.

High intensity focused ultrasound (HIFU) is widely used in medical practice, including cancer therapy. Also this approach is promising for remote release of encapsulated drugs in various other biomedical applications where local treatment is needed. Our approach underpins the minimization of HIFU impact on possible degradation of biological tissues and expand the use of HIFU in the controlled release of encapsulated drugs. We demonstrated the efficient ultrasound-induced release of labeled protein (Cy7-BSA) from elaborated nanocomposite microcapsules in vitro an in vivo. The capsule fabrication was done using combination of recently developed freezing-induced loading (FIL) technique and Layer-by-Layer assembly (LbL) used for the preparation of complex multilayer BSA/tannic acid nanocomposite capsules sensitive to HIFU. These capsules contain NIR fluorescent Cy7-labeled BSA in the shell for tracking in vivo and the high concentration of labels inside the capsules resulted in self-quenching provides the real-time detection of the protein once it is released from the capsule. Ultrasound-induced release in vivo of Cy7-labeled BSA initially quenched by magnetite nanoparticles was confirmed by fluorescent tomography. The significant decrease of Cy7 fluorescence under HIFU treatment in vitro was found to be due to a generation of reactive oxygen species and fast dye oxidation. Our results demonstrate that adapted HIFU setup can be used for the directed release of encapsulated substances in vivo under tissue compatible NIR monitoring by fluorescent tomography.

High-efficiency freezing-induced loading of inorganic nanoparticles and proteins into micron- and submicron-sized porous particles.

We demonstrate a novel approach to the controlled loading of inorganic nanoparticles and proteins into submicron- and micron-sized porous particles. The approach is based on freezing/thawing cycles, which lead to high loading densities. The process was tested for the inclusion of Au, magnetite nanoparticles, and bovine serum albumin in biocompatible vaterite carriers of micron and submicron sizes. The amounts of loaded nanoparticles or substances were adjusted by the number of freezing/thawing cycles. Our method afforded at least a three times higher loading of magnetite nanoparticles and a four times higher loading of protein for micron vaterite particles, in comparison with conventional methods such as adsorption and coprecipitation. The capsules loaded with magnetite nanoparticles by the freezing-induced loading method moved faster in a magnetic field gradient than did the capsules loaded by adsorption or coprecipitation. Our approach allows the preparation of multicomponent nanocomposite materials with designed properties such as remote control (e.g. via the application of an electromagnetic or acoustic field) and cargo unloading. Such materials could be used as multimodal contrast agents, drug delivery systems, and sensors.

In Vitro and in Vivo Visualization and Trapping of Fluorescent Magnetic Microcapsules in a Bloodstream.

Remote navigation and targeted delivery of biologically active compounds is one of the current challenges in the development of drug delivery systems. Modern methods of micro- and nanofabrication give us new opportunities to produce particles and capsules bearing cargo to deploy and possess magnetic properties to be externally navigated. In this work we explore multilayer composite magnetic microcapsules as targeted delivery systems in vitro and in vivo studies under natural conditions of living organism. Herein, we demonstrate magnetic addressing of fluorescent composite microcapsules with embedded magnetite nanoparticles in blood flow environment. First, the visualization and capture of the capsules at the defined blood flow by the magnetic field are shown in vitro in an artificial glass capillary employing a wide-field fluorescence microscope. Afterward, the capsules are visualized and successfully trapped in vivo into externally exposed rat mesentery microvessels. Histological analysis shows that capsules infiltrate small mesenteric vessels whereas large vessels preserve the blood microcirculation. The effect of the magnetic field on capsule preferential localization in bifurcation areas of vasculature, including capsule retention at the site once external magnet is switched off is discussed. The research outcome demonstrates that microcapsules can be effectively addressed in a blood flow, which makes them a promising delivery system with remote navigation by the magnetic field.

Nonuniform Growth of Composite Layer-by-Layer Assembled Coatings via Three-Dimensional Expansion of Hydrophobic Magnetite Nanoparticles.

Nanocomposite coatings are promising for a range of practical applications, and layer-by-layer assembly (LbL) is a versatile tool for nanocomposite formation. However, conventional LbL is a quite laborious procedure taking a lot of time to reach a sufficient thickness of the coatings required for practical applications. Herein, we proposed a novel variant of the LbL approach based on the deposition of hydrophilic polyelectrolyte molecules from a polar solvent and hydrophobic magnetite nanoparticles (NPs) from a nonpolar dispersion medium with an intermediate washing in the same polar solvent. The composite multilayers formed in this way exhibit exponential growth of the thickness and mass. On the basis of quartz crystal microbalance (QCM), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), atomic force microscopy (AFM), and surface profile measurements, we propose a model describing the driving force of multilayer formation and the factors leading to nonlinear growth of their mass and thickness. The results allow one to expand the understanding of the mechanism of the LbL assembly in order to form multifunctional nanocomposites in a more efficient way.

Effect of surface functionalization of metal wire on electrophysical properties of inductive elements.

The development of the microelectronics industry requires a new element basis with reduced size and increased functionality. The most important components in modern microelectronic integrated circuits are passive elements. One of the key challenges in order to improve the functionality of integrated circuits is to increase the quality of passive elements composing them. In this paper we suggest a novel approach to increase the quality factor Q of inductors by the surface modification and functionalization of the metal components. Ultrasound induced surface modification of metal wires led to the formation of a porous surface structure, which further can be functionalized with magnetite nanoparticles using layer-by-layer assembly technique. The surface modification and deposition of magnetite nanoparticles was investigated with SEM, XRD, and contact angle measurements. Additionally, inductance and resistance measurements, as the main parameters determining the Q-factor of inductors, were carried out. Samples with high number of magnetic nanoparticle-polyelectrolyte bilayers demonstrate a significant increase in inductance and a slight decrease in resistance in comparison to uncoated ones. The combination of these factors led to enhancement the Q-factor of the investigated inductive elements.