Eco-friendly chitosan microspheres as a novel one-step sorbent for the rapid purification and determination of pesticides and veterinary drug multi-residues in aquatic products with HPLC-MS/MS.

A modified QuEChERS method was developed to determine multi-class pesticide and veterinary residues in aquatic products. Chitosan microspheres were conveniently synthesized and utilized as the cleanup adsorbent in the QuEChERS procedure, showcasing rapid filtration one-step pretreatment ability for the determination of drug multi-residues in aquatic products. Compared to conventional synthetic sorbents, chitosan microspheres not only have good purification performance, but also have renewable and degradable properties. This novel sorbent worked well in the simultaneous determination of 95 pesticides and veterinary drug residues in aquatic products after being combined with an improved one-step vortex oscillating cleanup method. We achieved recoveries ranging from 64.0% to 115.9% for target drugs in shrimp and fish matrix. The limits of detection and quantification were 0.5-1.0 and 1.0-2.0 µg kg-1, respectively. Notably, hydrocortisone was detected with considerable frequency and concentration in the tested samples, underscoring the necessity for stringent monitoring of this compound in aquatic products.

Magnetic microbead-based upconversion immunoassay with laser-induced breakdown spectroscopy readout for the detection of prostate-specific antigen.

Laser-induced breakdown spectroscopy (LIBS) is a promising technique for the readout of immunochemical assays utilizing indirect detection of labels (Tag-LIBS), typically based on nanoparticles. We have previously demonstrated that Tag-LIBS immunoassay employing yttrium-based photon-upconversion nanoparticles (UCNPs) can reach sensitivity similar to commonly used enzyme and fluorescence immunoassays. In this study, we report on further increasing the sensitivity of UCNP-based Tag-LIBS immunoassay by employing magnetic microbeads (MBs) as the solid phase in the determination of cancer biomarker prostate-specific antigen. Due to the possibility of analyte preconcentration, MBs enabled achieving a limit of detection (LOD) of 4.0 pg·mL-1, representing two orders of magnitude improvement compared with equivalent microtiter plate-based assay (LOD of 460 pg·mL-1). In addition, utilizing MBs opens up the possibility of an internal standardization of the LIBS readout by employing iron spectral lines, which improves the assay robustness by compensating for LIBS signal fluctuations and bead-bound immunocomplexes lost throughout the washing steps. Finally, the practical applicability of the technique was confirmed by the successful analysis of clinical samples, showing a strong correlation with the standard electrochemiluminescence immunoassay. Overall, MB-based Tag-LIBS was confirmed as a promising immunoassay approach, combining fast readout, multiplexing possibilities, and high sensitivity approaching upconversion luminescence scanning while avoiding the requirement of luminescence properties of labels.

Quantitative CT imaging and radiation-absorbed dose estimations of 166Ho microspheres: paving the way for clinical application.

BACKGROUND: Microbrachytherapy enables high local tumor doses sparing surrounding tissues by intratumoral injection of radioactive holmium-166 microspheres (166Ho-MS). Magnetic resonance imaging (MRI) cannot properly detect high local Ho-MS concentrations and single-photon emission computed tomography has insufficient resolution. Computed tomography (CT) is quicker and cheaper with high resolution and previously enabled Ho quantification. We aimed to optimize Ho quantification on CT and to implement corresponding dosimetry. METHODS: Two scanners were calibrated for Ho detection using phantoms and multiple settings. Quantification was evaluated in five phantoms and seven canine patients using subtraction and thresholding including influences of the target tissue, injected amounts, acquisition parameters, and quantification volumes. Radiation-absorbed dose estimation was implemented using a three-dimensional 166Ho specific dose point kernel generated with Monte Carlo simulations. RESULTS: CT calibration showed a near-perfect linear relation between radiodensity (HU) and Ho concentrations for all conditions, with differences between scanners. Ho detection during calibration was higher using lower tube voltages, soft-tissue kernels, and without a scanner detection limit. The most accurate Ho recovery in phantoms was 102 ± 11% using a threshold of mean tissue HU + (2 × standard deviation) and in patients 98 ± 31% using a 100 HU threshold. Thresholding allowed better recovery with less variation and dependency on the volume of interest compared to the subtraction of a single HU reference value. Corresponding doses and histograms were successfully generated. CONCLUSION: CT quantification and dosimetry of 166Ho should be considered for further clinical application with on-site validation using radioactive measurements and intra-operative Ho-MS and dose visualizations. RELEVANCE STATEMENT: Image-guided holmium-166 microbrachytherapy currently lacks reliable quantification and dosimetry on CT to ensure treatment safety and efficacy, while it is the only imaging modality capable of quantifying high in vivo holmium concentrations. KEY POINTS: Local injection of 166Ho-MS enables high local tumor doses while sparing surrounding tissue. CT enables imaging-based quantification and radiation-absorbed dose estimation of concentrated Ho in vivo, essential for treatment safety and efficacy. Two different CT scanners and multiple acquisition and reconstruction parameters showed near-perfect linearity between radiodensity and Ho concentration. The most accurate Ho recoveries on CT were 102 ± 11% in five phantoms and 98 ± 31% in seven canine patients using thresholding methods. Dose estimations and volume histograms were successfully implemented for clinical application using a dose point kernel based on Monte Carlo simulations.

Sequential release of vancomycin and BMP-2 from chitosan/nano-hydroxyapatite thermosensitive hydrogel for the treatment of chronic osteomyelitis.

In this study, we developed scaffolds materials with microspheres to form a double sustained release system.Chitosan/nano-hydroxyapatite (CS-HA) was used as a drug carrier to construct a sustained-release system for Bone morphogenetic protein-2(BMP-2) and Vancomycin (VAN). Furthermore, VAN and BMP-2 loaded microspheres (Ms) were prepared by the emulsion ultrasonic method.The resultant composites were characterized by Scanning electron microscope (SEM), compressive strength, porosity, and biodegradation. The characterization results showed uniform porous and rough surface, enhanced thermal stability, and highest compressive strength ((1.912 ± 0.012) Kpa, the surface of the two microspheres was slightly folded and showed a regular spherical shape.The loading rate of BMP-2 was (59.611 × 10-4 ± 0.023 × 10-4)% and the encapsulation rate was (6.022 ± 0.005)%. The release rate of vancomycin and BMP-2 was 57.194% and 12.968% respectively. Osteogenic differentiation of Bone marrow mesenchymal stem cells (BMSCs) was confirmed by alkaline phosphatase quantification. The deposition of late osteogenic markers (calcium phosphates) detected by Alizarin red, which indicated extracellular matrix mineralization. The results showed that BMP-2/VAN in CS-HA hydrogel successfully achieved the sequential release of the double drugs, which could benefit bone regeneration.

Assemblable 3D biomimetic microenvironment for hMSC osteogenic differentiation.

Adequate simulation mimicking a tissue's native environment is one of the elemental premises in tissue engineering. Although various attempts have been made to induce human mesenchymal stem cells (hMSC) into an osteogenic pathway, they are still far from widespread clinical application. Most strategies focus primarily on providing a specific type of cue, inadequately replicating the complexity of the bone microenvironment. An alternative multifunctional platform for hMSC osteogenic differentiation has been produced. It is based on poly(vinylidene fluoride) (PVDF) and cobalt ferrites magnetoelectric microspheres, functionalized with collagen and gelatin, and packed in a 3D arrangement. This platform is capable of performing mechanical stimulation of piezoelectric PVDF, mimicking the bones electromechanical biophysical cues. Surface functionalization with extracellular matrix biomolecules and osteogenic medium complete this all-round approach. hMSC were cultured in osteogenic inducing conditions and tested for proliferation, surface biomarkers, and gene expression to evaluate their osteogenic commitment.

Eco-friendly, pH-sensitive curcumin-loaded sodium alginate/hydroxyapatite/quaternary ammonium chitosan microspheres with enhanced antibacterial and antioxidant activities for fruit preservation.

The development of intelligent responsive reactive packaging materials with natural polymers shows excellent potential in food preservation. In this study, eco-friendly, pH-sensitive sodium alginate (SA)/hydroxyapatite (HA)/quaternary ammonium chitosan (HACC) composite microspheres loading curcumin (CUR) with excellent antibacterial and antioxidant activities were successfully synthesized. Scanning electron microscopy (SEM) and nitrogen adsorption/desorption tests indicated that the doping of HA substantially increased the specific surface area and pore volume of the microspheres. The loading experiments showed that the efficiency of the microspheres was significantly increased by 49.47 % and 55.10 %, respectively, when HA and HACC were incorporated into the SA network. The release test results suggested that the release rate of SA/HA/HACC microspheres loading CUR (SA/HA/HACC@CUR) increased as the pH decreased, demonstrating notable pH-responsive release characteristics. DPPH free radical scavenging experiments demonstrated that the SA/HA/HACC@CUR had excellent and long-lasting antioxidant capacity. The antibacterial experiments revealed that the SA/HA/HACC@CUR had excellent antibacterial properties, with inhibition rates of 88.73 % and 92.52 % against E. coli and S. aureus, respectively. Making coatings out of microspheres could effectively slow down the rotting and deterioration of cherry tomatoes during storage, suggesting that microspheres with intelligent responses have a broad application prospect in fruit preservation.

Adsorption of haem by magnetic chitosan microspheres: Optimal conditions, adsorption mechanisms and density functional theory analyses.

Magnetic chitosan microspheres (Al@CTS@Fe3O4) were prepared for haem separation via chemical cross-linking of chitosan, Fe3O4 and AlCl3·6H2O. The properties of the Al@CTS@Fe3O4 microspheres were investigated through techniques including XRD, TEM, FTIR, BET analysis, SEM, TG, VSM, XPS and pHpzc analysis. The haem adsorption of Al@CTS@Fe3O4 was optimized via a Box-Behnken design (BBD) with three operating factors: Fe3O4 dose (0.5-1.3 g), AlCl3·6H2O concentration (0.25-1.25 mol/L) and glutaraldehyde dose (2-6 mL). The optimal haem adsorption effect was achieved with 1.1 g of Fe3O4, 0.75 mol/L AlCl3·6H2O, and 3 mL of glutaraldehyde. The adsorption kinetics and isotherms demonstrated that haem adsorption by the Al@CTS@Fe3O4 microspheres was best described by the pseudo-second-order model. The maximum adsorption capacity is 33.875 mg/g at pH 6. After six adsorption-desorption cycles, the removal of haem still reached 53.83 %. The surface adsorption mechanism of haem on Al@CTS@Fe3O4 can be attributed to electrostatic, hydrogen bonding, and n-π interactions. Thermodynamic calculations indicated that the adsorption process is spontaneous, with the microspheres preferentially accepting electrons and haem preferentially providing electrons. Consequently, the Al@CTS@Fe3O4 microspheres exhibit considerable potential as adsorbents for haem separation.

Spiral microchannels with concave cross-section for enhanced cancer cell inertial separation.

Inertial microfluidic technologies have proven effective for particle focusing and separation in many microchannels, typically the channels with the rectangular and trapezoidal shapes. To advance particle focusing in complex channels, we propose a spiral channel combining rectangular and concave cross-sections for high-resolution particle and cell focusing and separation. Numerical simulations were conducted to illustrate the effects of channel geometry on secondary flow distribution and particle focusing positions. The simulation shows the concave cross-section generates two asymmetrical Dean vortices skewing towards the inner and outer channel walls, resulting to stronger flow velocity magnitudes near the walls than the channel center. Consequently, larger particles focus near the inner wall, while smaller particles are trapped closer to the outer wall under the influence of the stronger velocity magnitude near the walls. A microfluidic chip with the proposed channel geometry, along with a traditional rectangular channel, was fabricated by 3D printing and PDMS casting. Fluorescent microbeads were used to investigate inertial focusing and separation behaviors in the microfluidic chips. Experimental results show that the concave channel facilitates particle focusing or trapping much closer to the walls than the traditional rectangular channel, achieving better separation resolution. Finally, the proposed channel was applied to separate lung cancer A549 cells from human blood, achieving a cancer cell recovery rate of ~ 84.78% (enrichment ratio over 820-fold) and a blood cell rejection rate of ~ 99.88%. This innovative channel design in inertial microfluidics offers new insights for enhanced particle focusing and holds significant promise for cell manipulation with improved separation resolution.

Breaking barriers in cancer management: The promising role of microsphere conjugates in cancer diagnosis and therapy.

Cancer is a significant worldwide health concern, and there is a demand for ongoing breakthroughs in treatment techniques. Microspheres are among the most studied drug delivery platforms for delivering cargo to a specified location over an extended period of time. They are biocompatible, biodegradable, and capable of surface modifications. Microspheres and their conjugates have emerged as potential cancer therapeutic options throughout the years. This review provides an in-depth look at the current advancements and applications of microspheres and their conjugates in cancer treatment. The review encompasses a wide array of conjugates, ranging from polymers such as ethyl cellulose and Eudragit to stimuli-responsive polymers, proteins, peptides, polysaccharides such as HA and chitosan, inorganic metals, aptamers, quantum dots (QDs), biomimetic conjugates, and radio conjugates designed for radioembolization. Conjugated microspheres precisely deliver chemotherapeutics to the intended target while achieving controlled drug release to prevent side effects. It offers a means of integrating several distinct therapeutic modalities (chemotherapy, photothermal therapy, photodynamic therapy, radiotherapy, immunotherapy, etc.) to provide synergistic effects during cancer treatment. This review offers insights into the prospects and evolving role of microspheres and their conjugates in the dynamic landscape of cancer therapy. This review provides a comprehensive resource for researchers and clinicians working towards advancements in cancer treatment through innovative applications in therapy and translational research.

Thermo-responsible PNIPAM-grafted polystyrene microspheres for mesenchymal stem cells culture and detachment.

The preparation of cells is a critical step in cell therapy. To ensure the effectiveness of cells used for clinical treatments, it is essential to harvest adherent cells from the culture media in a way that preserves their high viability and full functionality. In this study, we developed temperature-responsive poly(N-isopropylacrylamide) (PNIPAM)-grafted polystyrene (PS) microspheres using reversible addition-fragmentation chain transfer polymerization. These microspheres allow for the non-destructive harvesting of cultured cells through temperature changes. The composition and physicochemical properties of the PNIPAM-grafted PS microspheres were confirmed using infrared spectroscopy, elemental analysis, dynamic light scattering, and thermogravimetric analysis.In vitroexperiments demonstrated that these microspheres exhibit excellent biocompatibility, supporting the adhesion and proliferation of various cells. Moreover, the microspheres showed good temperature responsiveness in thermosensitive detachment experiments with GFP-HepG2cells and umbilical cord mesenchymal stem cells (UC-MSCs). Additionally, through orthogonal experiments, we identified a cell detachment aid mixture that significantly improved the dispersibility of cells detached from the microspheres, enhancing the efficiency of thermosensitive cell detachment by approximately 40%. The harvested UC-MSCs retained their capacity for re-proliferation and trilineage differentiation. Consequently, the temperature-responsive microspheres developed in this study, combined with the cell detachment aid mixtures, hold great potential for large-scale culture and harvesting of therapeutic cells in clinical applications.

Negatively Charged Thermosensitive Hydrogel Loaded with Pectin Microspheres to Recover the Mucosal Barrier for Ulcerative Colitis Therapy.

Ulcerative colitis (UC), a chronic inflammatory bowel disease, poses a heightened colorectal cancer risk due to persistent mucosal inflammation and barrier dysfunction. In this article, a negatively charged thermosensitive hydrogel loaded with pectin microspheres was used as the enema for UC treatment. Succinic acid was immobilized on poly(ε-caprolactone-co-glycolide)-poly(ethylene glycol)-poly(ε-caprolactone-co-glycolide) (PCLGA-PEG-PCLGA) triblock copolymers to preferentially coat on cationic-inflamed sites via electrostatic interaction for reconstructing the mucosal barrier. Anti-inflammation drug 5-aminosalicylic acid (5-ASA) and curcumin-loaded pectin microspheres (Pec@Cur) were dispersed in the hydrogel for the inflammatory treatment of UC. The thermally sensitive hydrogels were rectally injected into UC model mice. The hydrogel effectively adhered to ulcers and prolonged colon retention, enabling sustained drug release and remarkably relieving the symptoms of colitis. The negatively charged hydrogel exhibited excellent significance in the UC treatment.

Revitalizing elixir with orange peel amplification of alginate fish oil beads for enhanced anti-aging efficacy.

The research introduces a novel method for creating drug-loaded hydrogel beads that target anti-aging, anti-oxidative, and anti-inflammatory effects, addressing the interconnected processes underlying various pathological conditions. The study focuses on the development of hydrogel beads containing anti-aging compounds, antioxidants, and anti-inflammatory drugs to effectively mitigate various processes. The synthesis, characterization and in vitro evaluations, and potential applications of these multifunctional hydrogel beads are discussed. A polymeric alginate-orange peel extract (1:1) hydrogel was synthesized for encapsulating fish oil. Beads prepared with variable fish oil concentrations (0.1, 0.3, and 0.5 ml) were characterized, showing no significant decrease in size i.e., 0.5 mm and a reduction in pore size from 23 to 12 µm. Encapsulation efficiency reached up to 98% within 2 min, with controlled release achieved upto 45 to 120 min with increasing oil concentration, indicating potential for sustained delivery. Fourier-transform infrared spectroscopy confirmed successful encapsulation by revealing peak shifting, interaction between constituents. In vitro degradation studies showed the hydrogel's biodegradability improved from 30 to 120 min, alongside anti-inflammatory, anti-oxidative, anti-collagenase and anti-elastase activities, cell proliferation rate enhanced after entrapping fish oil. In conclusion, the synthesized hydrogel beads are a promising drug delivery vehicle because they provide stable and effective oil encapsulation with controlled release for notable anti-aging and regenerative potential. Targeted delivery for inflammatory and oxidative stress-related illnesses is one set of potential uses. Further research may optimize this system for broader applications in drug delivery and tissue engineering.

Long-Term Exposure to Polystyrene Microspheres and High-Fat Diet-Induced Obesity in Mice: Evaluating a Role for Microbiota Dysbiosis.

BACKGROUND: Microplastics (MPs) have become a global environmental problem, emerging as contaminants with potentially alarming consequences. However, long-term exposure to polystyrene microspheres (PS-MS) and its effects on diet-induced obesity are not yet fully understood. OBJECTIVES: We aimed to investigate the effect of PS-MS exposure on high-fat diet (HFD)-induced obesity and underlying mechanisms. METHODS: In the present study, C57BL/6J mice were fed a normal diet (ND) or a HFD in the absence or presence of PS-MS via oral administration for 8 wk. Antibiotic depletion of the microbiota and fecal microbiota transplantation (FMT) were performed to assess the influence of PS-MS on intestinal microbial ecology. We performed 16S rRNA sequencing to dissect microbial discrepancies and investigated the dysbiosis-associated intestinal integrity and inflammation in serum. RESULTS: Compared with HFD mice, mice fed the HFD with PS-MS exhibited higher body weight, liver weight, metabolic dysfunction-associated steatotic liver disease (MASLD) activity scores, and mass of white adipose tissue, as well as higher blood glucose and serum lipid concentrations. Furthermore, 16S rRNA sequencing of the fecal microbiota revealed that mice fed the HFD with PS-MS had greater α-diversity and greater relative abundances of Lachnospiraceae, Oscillospiraceae, Bacteroidaceae, Akkermansiaceae, Marinifilaceae, Deferribacteres, and Desulfovibrio, but lower relative abundances of Atopobiaceae, Bifidobacterium, and Parabacteroides. Mice fed the HFD with PS-MS exhibited lower expression of MUC2 mucin and higher levels of lipopolysaccharide and inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1ß, and IL-17A] in serum. Correlation analyses revealed that differences in the microbial flora of mice exposed to PS-MS were associated with obesity. Interestingly, microbiota-depleted mice did not show the same PS-MS-associated differences in Muc2 and Tjp1 expression in the distal colon, expression of inflammatory cytokines in serum, or obesity outcomes between HFD and HFD + PS-MS. Importantly, transplantation of feces from HFD + PS-MS mice to microbiota-depleted HFD-fed mice resulted in a lower expression of mucus proteins, higher expression of inflammatory cytokines, and obesity outcomes, similar to the findings in HFD + PS-MS mice. CONCLUSIONS: Our findings provide a new gut microbiota-driven mechanism for PS-MS-induced obesity in HFD-fed mice, suggesting the need to reevaluate the adverse health effects of MPs commonly found in daily life, particularly in susceptible populations. https://doi.org/10.1289/EHP13913.

Resorbable Microspheres versus Trisacryl Gelatin Microspheres for Uterine Artery Embolization: A Randomized Controlled Trial.

Background There are insufficient data comparing resorbable microspheres (RMs) with permanent trisacryl gelatin microspheres (TAGMs) for uterine artery embolization (UAE). Purpose To compare therapeutic efficacy and clinical outcomes in participants with symptomatic fibroids after UAE with RMs or TAGMs. Materials and Methods This randomized controlled trial included participants undergoing UAE for symptomatic fibroids at a single institution (from May 2021 to May 2023). Participants were randomized one-to-one to undergo UAE with either RMs or TAGMs. Numeric rating scale pain scores and cumulative fentanyl consumption were assessed for 24 hours after undergoing UAE. Anti-Mullerian hormone was measured to assess effects of UAE on ovarian function. MRI was performed before and 3 months after UAE to evaluate fibroid necrosis and uterine artery recanalization. Repeated variables such as pain were analyzed using Mann-Whitney U test with post hoc Bonferroni correction. Results Sixty female participants (mean age, 45.7 years ± 3.6 [SD]) completed the study, with 30 in each group. No evidence of a difference in pain scores was observed between groups (P > .99). Moreover, there was no evidence of a difference in the total fentanyl consumption at 24 hours after UAE between groups (median: RMs, 423 [IQR, 330-530] vs TAGMs, 562 [IQR, 437-780]; P = .15). Serum anti-Mullerian hormone 3 months after UAE showed no evidence of a difference between groups (RMs vs TAGMs, 0.71 ng/mL ± 0.73 vs 0.49 ng/mL ± 0.45, respectively; P = .09). No evidence of a difference in the rate of complete necrosis of the dominant fibroid was observed between groups (97% [29 of 30] for both groups; P > .99). The rate of uterine artery recanalization was higher in RM versus TAGM groups (70% [21 of 30] vs 17% [five of 30], respectively; P < .001). Conclusion UAE with RMs, compared with UAE with TAGMs, showed no evidence of a difference in terms of therapeutic effectiveness or postprocedural pain scores in participants with symptomatic fibroids. Clinical trial registration no. NCT05086770 © RSNA, 2024 See also the editorial by Spies in this issue.

Microbubbles bound to drug-eluting beads enable ultrasound imaging and enhanced delivery of therapeutics.

Transarterial chemoembolization (TACE) is an image-guided minimally invasive treatment for liver cancer which involves delivery of chemotherapy and embolic material into tumor-supplying arteries to block blood flow to a liver tumor and to deliver chemotherapy directly to the tumor. However, the released drug diffuses only less than a millimeter away from the beads. To enhance the efficacy of TACE, the development of microbubbles electrostatically bound to the surface of drug-eluting beads loaded with different amounts of doxorubicin (0-37.5 mg of Dox/mL of beads) is reported. Up to 400 microbubbles were bound to Dox-loaded beads (70-150 microns). This facilitated ultrasound imaging of the beads and increased the release rate of Dox upon exposure to high intensity focused ultrasound (HIFU). Furthermore, ultrasound exposure (1 MPa peak negative pressure) increased the distance at which Dox could be detected from beads embedded in a tissue-mimicking phantom, compared with a no ultrasound control.

A Magnetically Driven Biodegradable Microsphere with Mass Production Capability for Subunit Vaccine Delivery and Enhanced Immunotherapy.

Subunit vaccines have emerged as a promising strategy in immunotherapy for combating viral infections and cancer. Nevertheless, the clinical application of subunit vaccines is hindered by limitations in antigen delivery efficiency, characterized by rapid clearance and inadequate cellular uptake. Here, a novel subunit vaccine delivery system utilizing ovalbumin@magnetic nanoparticles (OVA@MNPs) encapsulated within biodegradable gelatin methacryloyl (GelMA) microspheres was proposed to enhance the efficacy of antigen delivery. OVA@MNPs-loaded GelMA microspheres, denoted as OMGMs, can be navigated through magnetic fields to deliver subunit vaccines into the lymphatic system efficiently. Moreover, the biodegradable OMGMs enabled the sustained release of subunit vaccines, concentrating OVA around lymph nodes and enhancing the efficacy of induced immune response. OMGMs were produced through a microfluidic droplet generation technique, enabling mass production. In murine models, OMGMs successfully accumulated antigens in lymph nodes abundant in antigen-presenting cells, leading to enhanced cellular and humoral immunity and pronounced antitumor effects with a single booster immunization. In conclusion, these findings highlight the promise of OMGMs as a practical subunit vaccination approach, thus addressing the limitations associated with antigen delivery efficiency and paving the way for advanced immunotherapeutic strategies.

Development of Alginate-Based Biodegradable Radioactive Microspheres Labeled with Positron Emitter through Click Chemistry Reaction: Stability and PET Imaging Study.

Biodegradable radioactive microspheres labeled with positron emitters hold significant promise for diagnostic and therapeutic applications in cancers and other diseases, including arthritis. The alginate-based polymeric microspheres offer advantages such as biocompatibility, biodegradability, and improved stability, making them suitable for clinical applications. In this study, we developed novel positron emission tomography (PET) microspheres using alginate biopolymer radiolabeled with gallium-68 (68Ga) through a straightforward conjugation reaction. Polyethylenimine (PEI)-decorated calcium alginate microspheres (PEI-CAMSs) were fabricated and further modified using azadibenzocyclooctyne-N-hydroxysuccinimide ester (ADIBO-NHS). Subsequently, azide-functionalized NOTA chelator (N3-NOTA) was labeled with [68Ga]Ga to obtain [68Ga]Ga-NOTA-N3, which was then reacted with the surface-modified PEI-CAMSs using strain-promoted alkyne-azide cycloaddition (SPAAC) reaction to develop [68Ga]Ga-NOTA-PEI-CAMSs, a novel PET microsphere. The radiolabeling efficiency and radiochemical stability of [68Ga]Ga-NOTA-PEI-CAMSs were determined using the radio-instant thin-layer chromatography-silica gel (radio-ITLC-SG) method. The in vivo PET images were also acquired to study the in vivo stability of the radiolabeled microspheres in normal mice. The radiolabeling efficiency of [68Ga]Ga-NOTA-PEI-CAMSs was over 99%, and the microspheres exhibited high stability (92%) in human blood serum. PET images demonstrated the stability and biodistribution of the microspheres in mice for up to 2 h post injection. This study highlights the potential of biodegradable PET microspheres for preoperative imaging and targeted radionuclide therapy. Overall, the straightforward synthesis method and efficient radiolabeling technique provide a promising platform for the development of theranostic microspheres using other radionuclides such as 90Y, 177Lu, 188Re, and 64Cu.

GAPDH-Silence Microsphere via Reprogramming Macrophage Metabolism and eradicating Bacteria for Diabetic infection bone regeneration.

Macrophage metabolism dysregulation, which is exacerbated by persistent stimulation in infectious and inflammatory diseases, such as diabetic infectious bone defects (DIBD), eventually leads to the failure of bone repair. Here, we have developed an injectable, macrophage-modulated GAPDH-Silence drug delivery system. This microsphere comprises chondroitin sulfate methacrylate (CM) and methacrylated gelatin (GM), while the dimethyl fumarate (DMF)-loaded liposome (D-lip) is encapsulated within the microsphere (CM@GM), named D-lip/CM@GM. Triggered by the over-expressed collagenase in DIBD, the microspheres degrade and release the encapsulated D-lip. D-lip could modulate metabolism by inhibiting GAPDH, which suppresses the over-activation of glycolysis, thus preventing the inflammatory response of macrophages in vitro. While beneficial for macrophages, D-lip/CM@GM is harmful to bacteria. GAPDH, while crucial for glycolysis of staphylococcal species (S. aureus), can be effectively countered by D-lip/CM@GM. We are utilizing existing drugs in innovative ways to target central metabolism for effective eradication of bacteria. In the DIBD model, our results confirmed that the D-lip/CM@GM enhanced bacteria clearance and reprogrammed dysregulated metabolism, thereby significantly improving bone regeneration. In conclusion, this GAPDH-Silence microsphere system may provide a viable strategy to promote diabetic infection bone regeneration.

Exploration of Curvature and Stiffness Dual-Regulated Breast Cancer Cell Motility by a Motor-Clutch Model and Cell Traction Force Characterization.

The migration of breast cancer cells is the main cause of death and significantly regulated by physical factors of the extracellular matrix (ECM). To be specific, the curvature and stiffness of the ECM were discovered to effectively guide cell migration in velocity and direction. However, it is not clear what the extent of effect is when these dual-physical factors regulate cell migration. Moreover, the mechanobiology mechanism of breast cancer cell migration in the molecular level and analysis of cell traction force (CTF) are also important, but there is a lack of systematic investigation. Therefore, we employed a microfluidic platform to construct hydrogel microspheres with an independently adjustable curvature and stiffness as a three-dimensional substrate for breast cancer cell migration. We found that the cell migration velocity was negatively correlated to curvature and positively correlated to stiffness. In addition, curvature was investigated to influence the focal adhesion expression as well as the assignment of F-actin at the molecular level. Further, with the help of a motor-clutch mathematical model and hydrogel microsphere stress sensors, it was concluded that cells perceived physical factors (curvature and stiffness) to cause changes in CTF, which ultimately regulated cell motility. In summary, we employed a theoretical model (motor-clutch) and experimental strategy (stress sensors) to understand the mechanism of curvature and stiffness regulating breast cancer cell motility. These results provide evidence of force driven cancer cell migration by ECM physical factors and explain the mechanism from the perspective of mechanobiology.

A Comparative Study of DC Beads, Callispheres and Multimodal Imaging Nano-Assembled Microspheres Loaded with Irinotecan in Vitro.

Introduction: In recent years, the development of drug-eluting embolization beads that can be imaged has become a hot research topic in regard to meeting clinical needs. In our previous study, we successfully developed nano-assembled microspheres (NAMs) for multimodal imaging purposes. NAMs can not only be visualized under CT/MR/Raman imaging but can also load clinically required doses of doxorubicin. It is important to systematically compare the pharmacokinetics of NAMs with those of commercially available DC Beads and CalliSpheres to evaluate the clinical application potential of NAMs. Methods: In our study, we compared NAMs with two types of drug-eluting beads (DEBs) in terms of irinotecan, drug-loading capacity, release profiles, microsphere diameter variation, and morphological characteristics. Results: Our results indicate that NAMs had an irinotecan loading capacity similar to those of DC Beads and CalliSpheres but exhibited better sustained release in vitro. Conclusion: NAMs have great potential for application in transcatheter arterial chemoembolization for the treatment of colorectal cancer liver metastases.