Functionalization and magnetonavigation of T-lymphocytes functionalized via nanocomposite capsules targeting with electromagnetic tweezers.

Modification of T-lymphocytes, which are capable of paracellular transmigration is a promising trend in modern personalized medicine. However, the delivery of required concentrations of functionalized T-cells to the target tissues remains a problem. We describe a novel method to functionalize T-cells with magnetic nanocapsules and target them with electromagnetic tweezers. T-cells were modified with the following magnetic capsules: Parg/DEX (150 nm), BSA/TA (300 nm), and BSA/TA (500 nm). T-cells were magnetonavigated in a phantom blood vessel capillary in cultural medium and in whole blood. The permeability of tumor tissues to captured T-cells was analyzed by magnetic delivery of modified T-cells to spheroids formed from 4T1 breast cancer cells. The dynamics of T-cell motion under a magnetic field gradient in model environments were analyzed by particle image velocimetry. The magnetic properties of the nanocomposite capsules and magnetic T-cells were measured. The obtained results are promising for biomedical applications in cancer immunotherapy.

Influence of protein nativity on the stability of bovine serum albumin coated microbubbles.

Protein-coated microbubbles have become one of the emerging platforms in biomedical research as theranostic agents. In recent years, microbubbles have been extensively used as ultrasound contrast agents and carriers of molecular cargoes, pertaining to which several studies have focused on tuning the properties of these bubbles to achieve a higher degree of biocompatibility and extended stability. Synthesis of microbubbles has so far been traditionally carried out with pre-heated proteins like bovine serum albumin (BSA) as shell coatings, owing to the ease in making BSA crosslinked structures through disulfide bridge formation. We, however, have performed experiments to demonstrate that air core microbubbles formed with native BSA are more stable compared with those formed using denatured BSA. The experimental observations have been supported with analytical modeling and computational studies, which offer insights into the effect of BSA conformation in stabilizing the microbubbles shells and prolonging their lifetimes.

Rapid synthesis of Pt(0) motors-microscrolls on a nickel surface via H2PtCl6-induced galvanic replacement reaction.

In this study, Pt(0) microscrolls are synthesized on polished Ni via galvanic replacement reaction (GRR). Employing in situ optical microscopy, the dynamic motion of the catalytic microscrolls as micromotors in H2O2 solutions is revealed. This method offers a rapid fabrication of scrolls from diverse noble metals and alloys.

Magnetically navigated microbubbles coated with albumin/polyarginine and superparamagnetic iron oxide nanoparticles.

While microbubbles (MB) are routinely used for ultrasound (US) imaging, magnetic MB are increasingly explored as they can be guided to specific sites of interest by applied magnetic field gradient. This requires the MB shell composition tuning to prolong MB stability and provide functionalization capabilities with magnetic nanoparticles. Hence, we developed air-filled MB stabilized by a protein-polymer complex of bovine serum albumin (BSA) and poly-L-arginine (pArg) of different molecular weights, showing that pArg of moderate molecular weight distribution (15-70 kDa) enabled MB with greater stability and acoustic response while preserving MB narrow diameters and the relative viability of THP-1 cells after 48 h of incubation. After MB functionalization with superparamagnetic iron oxide nanoparticles (SPION), magnetic moment values provided by single MB confirmed the sufficient SPION deposition onto BSA + pArg MB shells. During MB magnetic navigation in a blood vessel mimicking phantom with magnetic tweezers and in a Petri dish with adherent mouse renal carcinoma cell line, we demonstrated the effectiveness of magnetic MB localization in the desired area by magnetic field gradient. Magnetic MB co-localization with cells was further exploited for effective doxorubicin delivery with drug-loaded MB. Taken together, these findings open new avenues in control over albumin MB properties and magnetic navigation of SPION-loaded MB, which can envisage their applications in diagnostic and therapeutic needs.

Two-in-one sensor of refractive index and Raman scattering using hollow-core microstructured optical waveguides for colloid characterization.

Hollow-core microstructured optical waveguides (HC-MOW) have recently emerged in sensing technologies, including the gas and liquid detection for industrial as well as clinical applications. Antiresonant HC-MOW provide capabilities for applications in refractive index (RI) sensing, while the long optical path for analyte-light interaction in HC-MOW leads to increased sensitivity of sensor based on Raman scattering signal measurements. In this study, we developed a two-in-one sensor device using HC-MOW for RI and Raman scattering detection. The performance of the sensor was evaluated by characterizing protein-copolymer multicomponent colloids, specifically, bovine serum albumin (BSA) and poly(N - vinyl-2 -pyrrolidone-co-acrylic acid) P(VP-AA) nano-sized complexes and microbubbles of the corresponding shell. Monocomponent solutions showed linear dependencies of RI and characteristic Raman peak intensities on mass concentration. Multicomponent Raman sensing of BSA@P(VP-AA) complexes and microbubbles revealed that changes in P(VP-AA) characteristic peak intensities can describe interactions between components needed to produce colloid systems. RI sensing of multicomponent colloids demonstrated linear dependence on total mass concentrations for BSA@P(VP-AA) complexes, while corresponding BSA@P(VP-AA) microbubbles can be detected with concentrations as high as 4.0 × 108 MB/mL. Therefore, the developed two-in-one sensor of RI and Raman scattering can be used the robust characterization of albumin-based colloids designed for therapeutic and diagnostic needs.

Rapid low-cost hyperspectral imaging system for quantitative assessment of infantile hemangioma.

Hemangioma, the predominant benign tumor occurring in infancy, exhibits a wide range of prognoses and associated outcomes. The accurate determination of prognosis through noninvasive imaging modalities holds essential importance in enabling effective personalized treatment strategies and minimizing unnecessary surgical interventions for individual patients. The present study focuses on advancing the personalized prognosis of hemangioma by leveraging noninvasive optical sensing technologies by the development of a novel rapid hyperspectral sensor (image collection in 5 s, lateral resolution of 10 µm) that is capable of quantifying hemoglobin oxygenation and vascularization dynamics during the course of tumor evolution. We have developed a quantitative parameter for hemangioma assessment, that demonstrated agreement with the clinician's conclusion in 90% among all cases during clinical studies on six patients, who visited clinician from two to four times. The presented methodology has potential to be implemented as a supportive tool for accurate hemangioma diagnostics in clinics.

Membraneless Hydrogen Peroxide Fuel Cells as a Promising Clean Energy Source.

In an in-depth investigation of membraneless hydrogen peroxide-based fuel cells (H2O2 FCs), hydrogen peroxide (H2O2), a carbon-neutral compound, is demonstrated to undergo electrochemical decomposition to produce H2O, O2, and electrical energy. The unique redox properties of H2O2 position it as a viable candidate for sustainable energy applications. The proposed membraneless design addresses the limitations of conventional fuel cells, including fabrication complexities and design challenges. A novel three-dimensional electrode, synthesized via electroplating techniques, is introduced. Constructed from Au-electroplated carbon fiber cloth combined with Ni-foam, this electrode showcases enhanced electrochemical reaction kinetics, leading to an increased power density for H2O2 FCs. The performance of fuel cells is intricately linked to the pH levels of the electrolyte solution. Beyond FC applications, such electrodes hold potential in portable energy systems and as high surface area catalysts. This study emphasizes the significance of electrode engineering in optimizing the potential of H2O2 as an environmentally friendly energy source.

Bridging the gap: harnessing liquid nanomachine know-how for tackling harmful airborne particulates.

The emergence of "nanomotors", "nanomachines", and "nanorobotics" has transformed dynamic nanoparticle research, driving a transition from passive to active and intelligent nanoscale systems. This review examines two critical fields: the investigation of airborne particles, significant contributors to air pollution, and the rapidly emerging domain of catalytic and field-controlled nano- and micromotors. We examine the basic concepts of nano- and micromachines in motion and envision their possible use in a gaseous medium to trap and neutralize hazardous particulates. While past studies described the application of nanotechnology and nanomotors in various scenarios, airborne nano/micromachine motion and their control have yet to be thoroughly explored. This review intends to promote multidisciplinary research on nanomachines' propulsion and task-oriented applications, highlighting their relevance in obtaining a cleaner atmospheric environment, a critical component to consider for human health.

Full-optical photoacoustic imaging using speckle analysis and resolution enhancement by orthogonal pump patterns projection.

This paper presents an approach for achieving full optical photoacoustic imaging with enhanced resolution utilizing speckle pattern analysis. The proposed technique involves projecting patterns derived from binary masks corresponding to orthogonal functions onto the target to elicit a photoacoustic signal. The resulting signal is then recorded using a high-speed camera and analyzed using correlation analysis of the speckle motion. Our results demonstrate the feasibility of this optical approach to achieve imaging with enhanced resolution without the need for physical contact with the target, opening up new possibilities for non-invasive medical imaging and other applications.

Optoacoustic monitoring of bilirubin photodegradation.

Hematomas resulted from trauma are very common, and the efficacy of existing treatment techniques is limited. Phototherapy can be used to expedite healing and improve the appearance of the damaged tissue. Efficient phototherapy requires determination of chromophore composition in hematoma, which can be provided by the optoacoustic (OA) technique, as it combines high spatial resolution and optical contrast. Here, we conducted experiments on photodegradation of bilirubin in gelatin slin phantoms. We have demonstrated that the OA technique allows monitoring of bilirubin concentration during photodegradation, and also distinguishing bilirubin concentration in depth. The obtained results suggest that OA monitoring may be used for efficient hematoma phototherapy.

In Vivo Laser-Induced Vasoactive Microenvironmental Setting via a Stimuli-Responsive Microstructured Depot.

A stimuli-responsive polymeric three-dimensional microstructured film (PTMF) is a 3D structure with an array of sealed chambers on its external surface. In this work, we demonstrate the use of PTMF as a laser-triggered stimulus-response system for local in vivo targeted blood vessels stimulation by vasoactive substances. The native vascular networks of the mouse mesentery were used as model tissues. Epinephrine and KCl were used as vasoactive agents that were sealed into individual chambers upon precipitation in the amount of pictograms. We demonstrated the method for non-damaged one-by-one chamber activation using a focused 532 nm laser light passed through biological tissues. To avoid laser-induced photothermal damage to biological tissues, the PTMF was functionalized with Nile Red dye, which effectively absorbs laser light. Chemically stimulated blood vessel fluctuations were analyzed using digital image processing methods. Hemodynamics changes were measured and visualized using the particle image velocimetry approach.

Mucoadhesive Emulsion Microgels for Intravesical Drug Delivery: Preparation, Retention at Urothelium, and Biodistribution Study.

The intravesical instillation procedure is a proven method in modern urology for the treatment of bladder diseases. However, the low therapeutic efficiency and painfulness of the instillation procedure are significant limitations of this method. In the present study, we propose an approach to solving this problem by using microsized mucoadhesive macromolecular carriers based on whey protein isolate with the possibility of prolonged release of drugs as a drug delivery system. The optimal water-to-oil ratio (1:3) and whey protein isolate concentration (5%) were determined to obtain emulsion microgels with sufficient loading efficiency and mucoadhesive properties. The droplet diameter of emulsion microgels varies from 2.2 to 3.8 µm. The drug release kinetics from the emulsion microgels was evaluated. The release of the model dye in saline and artificial urine in vitro was observed for 96 h and reached up to 70% of loaded cargo for samples. The effect of emulsion microgels on the morphology and viability of two cell lines was observed: L929 mouse fibroblasts (normal adherent cells) and THP-1 human monocytes (cancer suspension cells). Developed emulsion microgels (5%, 1:3 and 1:5) showed sufficient mucoadhesion to a porcine bladder urothelium ex vivo. The biodistribution of emulsion microgels (5%, 1:3 and 1:5) in mice (n = 3) after intravesical (instillation) and systemic (intravenous) administration was assessed in vivo and ex vivo using near-infrared fluorescence live imaging for real time. It was demonstrated that intravesical instillation allows approximately 10 times more efficient accumulation of emulsion microgels in the mice urinary bladder in vivo 1 h after injection compared to systemic injection. The retention of the emulsion of mucoadhesive microgels in bladders after the intravesical instillation was observed for 24 h.

Revealing the static and dynamic nanomechanical properties of diatom frustules-Nature's glass lace.

Diatoms are single cell microalgae enclosed in silica exoskeletons (frustules) that provide inspiration for advanced hybrid nanostructure designs mimicking multi-scale porosity to achieve outstanding mechanical and optical properties. Interrogating the structure and properties of diatoms down to nanometer scale leads to breakthrough advances reported here in the nanomechanical characterization of Coscinodiscus oculus-iridis diatom pure silica frustules, as well as of air-dried and wet cells with organic content. Static and dynamic mode Atomic Force Microscopy (AFM) and in-SEM nanoindentation revealed the peculiarities of diatom response with separate contributions from material nanoscale behavior and membrane deformation of the entire valve. Significant differences in the nanomechanical properties of the different frustule layers were observed. Furthermore, the deformation response depends strongly on silica hydration and on the support from the internal organic content. The cyclic loading revealed that the average compliance of the silica frustule is 0.019 m/N and increases with increasing number of cycles. The structure-mechanical properties relationship has a direct impact on the vibrational properties of the frustule as a complex micrometer-sized mechanical system. Lessons from Nature's nanostructuring of diatoms open up pathways to new generations of nano- and microdevices for electronic, electromechanical, photonic, liquid, energy storage, and other applications.

Hydrogel-Inducing Graphene-Oxide-Derived Core-Shell Fiber Composite for Antibacterial Wound Dressing.

The study reveals the polymer-crosslinker interactions and functionality of hydrophilic nanofibers for antibacterial wound coatings. Coaxial electrospinning leverages a drug encapsulation protocol for a core-shell fiber composite with a core derived from polyvinyl alcohol and polyethylene glycol with amorphous silica (PVA-PEG-SiO2), and a shell originating from polyvinyl alcohol and graphene oxide (PVA-GO). Crosslinking with GO and SiO2 initiates the hydrogel transition for the fiber composite upon contact with moisture, which aims to optimize the drug release. The effect of hydrogel-inducing additives on the drug kinetics is evaluated in the case of chlorhexidine digluconate (CHX) encapsulation in the core of core-shell fiber composite PVA-PEG-SiO2-1x-CHX@PVA-GO. The release rate is assessed with the zero, first-order, Higuchi, and Korsmeyer-Peppas kinetic models, where the inclusion of crosslinking silica provides a longer degradation and release rate. CHX medicated core-shell composite provides sustainable antibacterial activity against Staphylococcus aureus.

Noninvasive, continuous fluorescence monitoring of bilirubin photodegradation.

Nowadays phototherapy is widely used for treatment of various diseases. However, efficient application of phototherapy requires an understanding of light interactions with main endogenous chromophores (e.g., hemoglobin, bilirubin, and water) in tissue. In particular, bilirubin is the target chromophore in the treatment of neonatal jaundice, which is the most common disease affecting up to 80% of preterm infants. The most frequently recommended treatment technique for this disease is phototherapy with blue light in combination with conventional drug therapy. To follow threshold total serum bilirubin (TSB) concentration guidelines, it is essential to estimate TSB concentration accurately. The gold standard biochemical analysis is invasive and bulky. Moreover, noninvasive methods do not provide sufficient reproducibility and accuracy. In this research, the fluorescence sensing of bilirubin with human serum albumin complexes was studied. The fluorescence time course during light irradiation (central wavelength: 467 nm and power density: 12.13 mW cm-2) was demonstrated to depend on the initial concentration. Specifically, for the bilirubin concentration C = 18.65 µM, an insignificant fluorescence signal increase was observed during the first 30 minutes of light irradiation, while for bilirubin concentration C = 373 µM, the fluorescence signal did not reach maximum during 2.5 hours of light irradiation. Thus, fluorescence sensing might show increased accuracy when used with other noninvasive bilirubin sensing methods.

Plug-and-Play Lymph Node-on-Chip: Secondary Tumor Modeling by the Combination of Cell Spheroid, Collagen Sponge and T-Cells.

Towards the improvement of the efficient study of drugs and contrast agents, the 3D microfluidic platforms are currently being actively developed for testing these substances and particles in vitro. Here, we have elaborated a microfluidic lymph node-on-chip (LNOC) as a tissue engineered model of a secondary tumor in lymph node (LN) formed due to the metastasis process. The developed chip has a collagen sponge with a 3D spheroid of 4T1 cells located inside, simulating secondary tumor in the lymphoid tissue. This collagen sponge has a morphology and porosity comparable to that of a native human LN. To demonstrate the suitability of the obtained chip for pharmacological applications, we used it to evaluate the effect of contrast agent/drug carrier size, on the penetration and accumulation of particles in 3D spheroids modeling secondary tumor. For this, the 0.3, 0.5 and 4 µm bovine serum albumin (BSA)/tannic acid (TA) capsules were mixed with lymphocytes and pumped through the developed chip. The capsule penetration was examined by scanning with fluorescence microscopy followed by quantitative image analysis. The results show that capsules with a size of 0.3 µm passed more easily to the tumor spheroid and penetrated inside. We hope that the device will represent a reliable alternative to in vivo early secondary tumor models and decrease the amount of in vivo experiments in the frame of preclinical study.

Targeted Therapy for Glomerulonephritis Using Arterial Delivery of Encapsulated Etanercept.

Complex immunosuppressive therapy is prescribed in medical practice to patients with glomerulonephritis to help them overcome symptoms and prevent chronic renal failure. Such an approach requires long-term systemic administration of strong medications, which causes severe side effects. This work shows the efficiency of polymer capsule accumulation (2.8 ± 0.4 µm) containing labeled etanercept (100 µg per dose) in the kidneys of mice. The comparison of injection into the renal artery and tail vein shows the significant superiority of the intra-arterial administration strategy. The etanercept retention rate of 18% and 8% ID in kidneys was found 1 min and 1 h after injection, respectively. The capsules were predominantly localized in the glomeruli after injection in mice using a model of acute glomerulonephritis. Histological analysis confirmed a significant therapeutic effect only in animals with intra-arterial administration of microcapsules with etanercept. The proposed strategy combines endovascular surgery and the use of polymer microcapsules containing a high molecular weight drug that can be successfully applied to treat a wide range of kidney diseases associated with glomerular pathology.

In Situ Monitoring of Layer-by-Layer Assembly Surface Modification of Nanophotonic-Microfluidic Sensor.

An elaboration of the photonic based sensors is the most promising direction in modern analytical chemistry from the point of view of real clinical applications. The highest sensitivity is demonstrated by sensors based on photonic integrated circuits (PICs). This type of sensor has been recently successfully combined with microfluidics, which decreased the analyte volume for analysis down to microliter units. The most significant disadvantage regarding these photonic sensors is low specificity. One of the methods that could be useful for such type of problem is the layer by layer (LBL) assembly. The peculiarity of a PIC based sensor is the ability to precisely control surface modification by using measurements of a minimum resonance position shift. The bovine serum albumin (BSA) and tannic acid (TA) molecules were selected for LBL assembly because on one side they form a stable LBL assembly film based on hydrogen bonds, while the other side of both TA and BSA molecules can be used for conjugation with target molecules. A microring resonator (MRR) and a Mach-Zehnder interferometer (MZI) based on a silicon nitride platform combined with a microfluidic system were elaborated and used for monitoring the LBL film assembly. Obtained results have a good correlation with measurements carried out by atom force microscopy. Thus, the ability of using PIC based sensors for in situ control of surface modification was demonstrated and can be considered in point-of-care (POC) devices that have a very good perspective for both early pathological state diagnosis and evaluation of treatment efficiency.

Engineered multicompartment vesicosomes for selective uptake by living cells.

Small extracellular vesicles (sEVs) have attracted tremendous interest in recent years due to their exceptional properties for therapeutic and diagnostic applications. Although much research was focused on the quantity and content of sEVs, less efforts have been put into discovering the interaction between sEVs and cells. Here we engineered multicompartment particles, termed vesicosomes, by deposition of sEVs derived from MCF7, CHO cells and human plasma onto the surface of polyelectrolyte (PE)-coated silica (SiO2) microparticles. Uptake of the PE-coated SiO2 microparticles by parent cells was significantly enhanced by coating them with sEVs, compared to PE-coated SiO2 microparticles independent of the terminated polyelectrolyte layer. This study highlights the emerging role of sEVs membrane receptors in the sEV-cells interaction and demonstrates the potential application of sEV-like multicompartment particles as therapeutic carriers.

Albumin microbubbles conjugated with zinc and aluminum phthalocyanine dyes for enhanced photodynamic activity.

Gas-liquid interfaces are reaching a particular interest in biomedicine. Microbubbles, ultrasound contrast agents of clinical routine, gained increasing attention as theranostic platforms due to the preserved acoustic response, drug conjugation capabilities, and applicability in biological barrier opening. A combination of microbubbles and photodynamic therapy agents can enhance the photodynamic effect, yet the evaluation of agent conjugation on microbubble stabilization and photodynamic effect is needed. Hence, two commercially available phthalocyanine photosensitizers - Holosens® (ZnPc) and Photosens® (AlPc) - were coupled with bovine serum albumin before microbubble synthesis. We demonstrated an albumin: phthalocyanine ratio of 1:1 and covalent attachment for ZnPc, a ratio of 1:3 with electrostatic binding for AlPc. Submicron-sized microbubbles (air- and SF6- filled) had a diameter of 0.8 µm. Albumin-phthalocyanine conjugates increased the microbubble concentration and shelf-life stability compared to plain ones. We hypothesized that phthalocyanine fluorescence lifetime values decreased after conjugation with microbubbles due to narrow distance between conjugates in the shell. Agents based on AlPc demonstrated higher photodynamic activity than agents based on ZnPc, and microbubbles preserved acoustic stability in human blood plasma. The biodistribution of AlPc-conjugated microbubbles was evaluated. We conclude that our microbubble platforms demonstrate greater photodynamic activity and prolonged stability for further applications in photodynamic therapy.