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Hellenic Journal of Nuclear Medicine 2020The current review unfolds the procedural steps and the clinical evidence for yttrium-90 (Y)-microspheres radioembolization. Radioembolization is part of the... (Review)
Review
The current review unfolds the procedural steps and the clinical evidence for yttrium-90 (Y)-microspheres radioembolization. Radioembolization is part of the loco-regional therapeutic spectrum for liver malignancy and involves the invasive, intra-arterial delivery of microspheres carrying β-emitter isotopes in order to destroy cancerous tissue via ionizing radiation. The main steps of the therapeutic process are selection of eligible patients, angiographic workup, simulation scintigraphy, pre-treatment dosimetry, actual treatment and post-treatment imaging/dosimetry. Radioembolization is routinely applied in advanced stage hepatocellular carcinoma (HCC), yet its role is being investigated even in earlier stages. Prospective, randomized controlled trials did not verify increased overall survival of radioembolization over systemic treatment with sorafenib in HCC; however, it showed survival benefit in certain sub-groups and a favorable toxicity profile with fewer adverse events. Radioembolization is also applied in metastatic colon cancer showing tumoral liver responses, which however did not translate into an overall survival benefit. Data regarding applications of this method in other neoplasms, such as neuroendocrine tumors, breast cancer and melanoma are also presented. There are ongoing clinical trials to define the role of radioembolization within recent treatments algorithms, to determine optimal combinations of this treatment with systemic and targeted therapies and to decide the patients' sub-groups, who will benefit the most.
Topics: Carcinoma, Hepatocellular; Embolization, Therapeutic; Humans; Liver Neoplasms; Microspheres; Yttrium Radioisotopes
PubMed: 33306761
DOI: 10.1967/s002449912210 -
ACS Applied Bio Materials Feb 2022Three-dimensional cellular constructs derived from pluripotent stem cells allow the study of neurodevelopment and neurological disease within a spatially organized...
Three-dimensional cellular constructs derived from pluripotent stem cells allow the study of neurodevelopment and neurological disease within a spatially organized model. However, the robustness and utility of three-dimensional models is impacted by tissue self-organization, size limitations, nutrient supply, and heterogeneity. In this work, we have utilized the principles of nanoarchitectonics to create a multifunctional polymer/bioceramic composite microsphere system for stem cell culture and differentiation in a chemically defined microenvironment. Microspheres could be customized to produce three-dimensional structures of defined size (ranging from >100 to <350 μm) with lower mechanical properties compared with a thin film. Furthermore, the microspheres softened in solution, approaching more tissue-like mechanical properties over time. With neural stem cells (NSCs) derived from human induced pluripotent stem cells, microsphere-cultured NSCs were able to utilize multiple substrates to promote cell adhesion and proliferation. Prolonged culture of NSC-bound microspheres under differentiating conditions allowed the formation of both neural and glial cell types from control and patient-derived stem cell models. Human NSCs and differentiated neurons could also be cocultured with astrocytes and human umbilical vein endothelial cells, demonstrating application for tissue-engineered modeling of development and human disease. We further demonstrated that microspheres allow the loading and sustained release of multiple recombinant proteins to support cellular maintenance and differentiation. While previous work has principally utilized self-organizing models or protein-rich hydrogels for neural culture, the three-dimensional matrix developed here through nanoarchitectonics represents a chemically defined and robust alternative for the study of neurodevelopment and nervous system disorders.
Topics: Endothelial Cells; Humans; Induced Pluripotent Stem Cells; Microspheres; Nervous System Diseases; Neural Stem Cells
PubMed: 35045249
DOI: 10.1021/acsabm.1c01012 -
Nature Communications Mar 2022Drug delivery systems with high content of drug can minimize excipients administration, reduce side effects, improve therapeutic efficacy and/or promote patient...
Drug delivery systems with high content of drug can minimize excipients administration, reduce side effects, improve therapeutic efficacy and/or promote patient compliance. However, engineering such systems is extremely challenging, as their loading capacity is inherently limited by the compatibility between drug molecules and carrier materials. To mitigate the drug-carrier compatibility limitation towards therapeutics encapsulation, we developed a sequential solidification strategy. In this strategy, the precisely controlled diffusion of solvents from droplets ensures the fast in-droplet precipitation of drug molecules prior to the solidification of polymer materials. After polymer solidification, a mass of drug nanoparticles is embedded in the polymer matrix, forming a nano-in-micro structured microsphere. All the obtained microspheres exhibit long-term storage stability, controlled release of drug molecules, and most importantly, high mass fraction of therapeutics (21.8-63.1 wt%). Benefiting from their high drug loading degree, the nano-in-micro structured acetalated dextran microspheres deliver a high dose of methylprednisolone (400 μg) within the limited administration volume (10 μL) by one single intrathecal injection. The amount of acetalated dextran used was 1/433 of that of low drug-loaded microspheres. Moreover, the controlled release of methylprednisolone from high drug-loaded microspheres contributes to improved therapeutic efficacy and reduced side effects than low drug-loaded microspheres and free drug in spinal cord injury therapy.
Topics: Drug Carriers; Drug Delivery Systems; Humans; Microspheres; Polymers; Solvents; Spinal Cord Injuries
PubMed: 35273148
DOI: 10.1038/s41467-022-28787-7 -
Molecules (Basel, Switzerland) Jun 2021Inert microspheres, labeled with several radionuclides, have been developed during the last two decades for the intra-arterial treatment of liver tumors, generally... (Review)
Review
Inert microspheres, labeled with several radionuclides, have been developed during the last two decades for the intra-arterial treatment of liver tumors, generally called Selective Intrahepatic radiotherapy (SIRT). The aim is to embolize microspheres into the hepatic capillaries, accessible through the hepatic artery, to deliver high levels of local radiation to primary (such as hepatocarcinoma, HCC) or secondary (metastases from several primary cancers, e.g., colorectal, melanoma, neuro-endocrine tumors) liver tumors. Several types of microspheres were designed as medical devices, using different vehicles (glass, resin, poly-lactic acid) and labeled with different radionuclides, Y and Ho. The relationship between the microspheres' properties and the internal dosimetry parameters have been well studied over the last decade. This includes data derived from the clinics, but also computational data with various millimetric dosimetry and radiobiology models. The main purpose of this paper is to define the characteristics of these radiolabeled microspheres and explain their association with the microsphere distribution in the tissues and with the clinical efficacy and toxicity. This review focuses on avenues to follow in the future to optimize such particle therapy and benefit to patients.
Topics: Embolization, Therapeutic; Holmium; Humans; Microspheres; Neoplasms; Radiopharmaceuticals; Yttrium Radioisotopes
PubMed: 34209590
DOI: 10.3390/molecules26133966 -
Journal of Clinical Virology : the... Jan 2021Heartland virus (HRTV), a recently reclassified member of the genus Bandavirus, family Phenuiviridae, was first isolated in 2009 from a Missouri farmer exhibiting...
BACKGROUND
Heartland virus (HRTV), a recently reclassified member of the genus Bandavirus, family Phenuiviridae, was first isolated in 2009 from a Missouri farmer exhibiting leukopenia and thrombocytopenia with suspected ehrlichiosis. Since then, more HRTV cases have been diagnosed, and firstline laboratory diagnostic assays are needed to identify future infections Objectives. We sought to develop rapid and reliable IgM and IgG microsphere immunoassays (MIAs) to test sera of patients suspected of having HRTV infection, and to distinguish between recent and past infections.
STUDY DESIGN
Heartland virus antigen was captured by an anti-HRTV monoclonal antibody covalently bound to microspheres. Antibodies in human sera from confirmed HRTV-positive and negative cases were reacted with the microsphere complexes and detected using a BioPlex® 200 instrument. Assay cutoffs were determined by receiver operator characteristic analysis of the normalized test output values, equivocal zones for each assay were defined, and sensitivities, specificities, accuracies, and imprecision values were calculated.
RESULTS
Sensitivities, specificities and accuracies of the IgM and IgG MIAs were all >95 %. Both tests were precise within and between assay plates, and cross-reactivity with other arboviruses was not observed.
CONCLUSIONS
HRTV IgM and IgG MIAs are accurate and rapid first-line methods to serologically identify recent and past HRTV infections.
Topics: Antibodies, Viral; Antigens, Viral; Cross Reactions; Humans; Immunoassay; Immunoglobulin M; Microspheres; Phlebovirus
PubMed: 33248359
DOI: 10.1016/j.jcv.2020.104693 -
Zhongguo Xiu Fu Chong Jian Wai Ke Za... Aug 2023To prepare a novel hyaluronic acid methacrylate (HAMA) hydrogel microspheres loaded polyhedral oligomeric silsesquioxane-diclofenac sodium (POSS-DS) patricles, then...
OBJECTIVE
To prepare a novel hyaluronic acid methacrylate (HAMA) hydrogel microspheres loaded polyhedral oligomeric silsesquioxane-diclofenac sodium (POSS-DS) patricles, then investigate its physicochemical characteristics and and biological properties.
METHODS
Using sulfhydryl POSS (POSS-SH) as a nano-construction platform, polyethylene glycol and DS were chemically linked through the "click chemistry" method to construct functional nanoparticle POSS-DS. The composition was analyzed by nuclear magnetic resonance spectroscopy and the morphology was characterized by transmission electron microscopy. In order to achieve drug sustained release, POSS-DS was encapsulated in HAMA, and hybrid hydrogel microspheres were prepared by microfluidic technology, namely HAMA@POSS-DS. The morphology of the hybrid hydrogel microspheres was characterized by optical microscope and scanning electron microscope. The degradation and drug release efficiency were observed. Cell counting kit 8 (CCK-8) and live/dead staining were used to detect the effect on chondrocyte proliferation. Moreover, a chondrocyte inflammation model was constructed and cultured with HAMA@POSS-DS. The relevant inflammatory indicators, including collagen type Ⅱ, aggrecan (AGG), matrix metalloproteinase 13 (MMP-13), recombinant A disintegrin and metalloproteinase with thrombospondin 5 (Adamts5), and recombinant tachykinin precursor 1 (TAC1) were detected by immunofluorescence staining and real-time fluorescence quantitative PCR, with normal cultured chondrocytes and the chondrocyte inflammation model without treatment as control group and blank group respectively to further evaluate their anti-inflammatory activity. Finally, by constructing a rat model of knee osteoarthritis, the effectiveness of HAMA@POSS-DS on osteoarthritis was evaluated by X-ray film and Micro-CT examination.
RESULTS
The overall particle size of POSS-DS nanoparticles was uniform with a diameter of about 100 nm. HAMA@POSS-DS hydrogel microspheres were opaque spheres with a diameter of about 100 μm and a spherical porous structure. The degradation period was 9 weeks, during which the loaded POSS-DS nanoparticles were slowly released. CCK-8 and live/dead staining showed no obvious cytotoxicity at HAMA@POSS-DS, and POSS-DS released by HAMA@POSS-DS significantly promoted cell proliferation (<0.05). In the chondrocyte anti-inflammatory experiment, the relative expression of collagen type Ⅱ mRNA in HAMA@POSS-DS group was significantly higher than that in control group and blank group (<0.05). The relative expression level of AGG mRNA was significantly higher than that of blank group (<0.05). The relative expressions of MMP-13, Adamts5, and TAC1 mRNA in HAMA@POSS-DS group were significantly lower than those in blank group (<0.05). experiments showed that the joint space width decreased after operation in rats with osteoarthritis, but HAMA@POSS-DS delayed the process of joint space narrowing and significantly improved the periarticular osteophytosis (<0.05).
CONCLUSION
HAMA@POSS-DS can effectively regulate the local inflammatory microenvironment and significantly promote chondrocyte proliferation, which is conducive to promoting cartilage regeneration and repair in osteoarthritis.
Topics: Animals; Rats; Matrix Metalloproteinase 13; Microspheres; Hydrogels; Collagen Type II; Diclofenac; Inflammation; Osteoarthritis, Knee; Hyaluronic Acid; Aggrecans
PubMed: 37586790
DOI: 10.7507/1002-1892.202302105 -
Biomaterials Science May 2022Heart disease is the leading cause of death globally, and delivery of therapeutic cargo (, particles loaded with proteins, drugs, or genes and cells) through direct...
Heart disease is the leading cause of death globally, and delivery of therapeutic cargo (, particles loaded with proteins, drugs, or genes and cells) through direct injection into the myocardium is a promising clinical intervention. However, retention of deliverables to the contracting myocardium is low, with as much as 60-90% of payload being lost within 24 hr. Commercially-available injectable hydrogels, including Matrigel, have been hypothesized to increase payload retention but have not yielded significant improvements in quantified analyses. Here, we assess a recombinant hydrogel composed of chemically modified hyaluronan and elastin-like protein (HELP) as an alternative injectable carrier to increase cargo retention. HELP is crosslinked using dynamic covalent bonds, and tuning the hyaluronan chemistry significantly alters hydrogel mechanical properties including stiffness, stress relaxation rate, and ease of injectability through a needle or catheter. These materials can be injected even after complete crosslinking, extending the time window for surgical delivery. We show that HELP gels significantly improve retention of microsphere cargo compared to Matrigel, both 1 day and 7 days post-injection directly into the rat myocardium. These data suggest that HELP gels may assist with the clinical translation of therapeutic cargo designed for delivery into the contracting myocardium by preventing acute cargo loss.
Topics: Animals; Elastin; Hyaluronic Acid; Hydrogels; Microspheres; Myocardium; Rats
PubMed: 35411353
DOI: 10.1039/d1bm01890f -
The Chinese Journal of Dental Research Mar 2022Microspheres have been widely utilised as versatile carriers in biomedical applications. In recent years, as a new type of injectable scaffold, microspheres have...
Microspheres have been widely utilised as versatile carriers in biomedical applications. In recent years, as a new type of injectable scaffold, microspheres have attracted increasing attention in the field of regenerative medicine owing to their various advantages including their small size, large specific surface area and mimicry of the 3D native environment. These characteristics enable them to adopt the narrow and irregular anatomy of the tooth and become an ideal scaffold for endodontic regeneration. Microspheres play an important role in carrying biologics (cells, biomolecules and drugs), which effectively regulate the fate of stem cells and control the release of growth factors and drugs. Cell-laden microspheres, which can be divided into microcarriers and microcapsules, have great application prospects in dental pulp regeneration. This paper summarises the properties and characteristics of microsphere scaffolds used in tissue engineering, placing emphasis on their advantages and applications in endodontic regeneration.
Topics: Dental Pulp; Microspheres; Regeneration; Regenerative Medicine; Tissue Engineering
PubMed: 35293708
DOI: 10.3290/j.cjdr.b2752709 -
Advanced Science (Weinheim,... Jun 2023Resolving inflammation and promoting intestinal tissue regeneration are critical for inflammatory bowel disease (IBD) treatment. Bioactive glass (BG) is a clinically...
Resolving inflammation and promoting intestinal tissue regeneration are critical for inflammatory bowel disease (IBD) treatment. Bioactive glass (BG) is a clinically approved bone graft material and has been shown to modulate inflammatory response, but it is unknown whether BG can be applied to treat IBD. Here, it is reported that BG attenuates pro-inflammatory response of lipopolysaccharide (LPS)-stimulated macrophages and hence reduces inflammatory damage to intestinal organoids in vitro. In addition, zein/sodium alginate-based core-shell microspheres (Zein/SA/BG) are developed for oral delivery of BG, which helps prevent premature dissolution of BG in the stomach. The results show that Zein/SA/BG protects BG from a gastric-simulated environment while dissolved in an intestinal-simulated environment. When administered to acute and chronic colitis mice model, Zein/SA/BG significantly reduces intestinal inflammation, promotes epithelial tissue regeneration, and partially restores microbiota homeostasis. These findings are the first to reveal the therapeutic efficacy of BG against IBD, which may provide a new therapeutic approach at low cost for effective IBD treatment.
Topics: Mice; Animals; Microspheres; Hydrogels; Zein; Inflammatory Bowel Diseases; Inflammation
PubMed: 37092589
DOI: 10.1002/advs.202207418 -
Journal of Immunology Research 2019Detection and analysis of antigen-antibody reaction is one of the most critical detection techniques in the fields of medicine, biology, environmental science, and food... (Review)
Review
Detection and analysis of antigen-antibody reaction is one of the most critical detection techniques in the fields of medicine, biology, environmental science, and food safety. Traditional and classical methods for detecting antigen and antibody encounter many problems, such as time-consuming, high cost, and low accuracy. A novel immune microsphere imaging technique by the microlens is used to test the changes of refractive index before and after antigen-antibody reaction. It can quickly perform qualitative and quantitative determination for antigen-antibody reaction without any labeling, premodification, postwashing, and expensive enzymes. Here, we feature and discuss its principle and advantages, structure of a microlens immunoassay instrument, and potential in measuring clinical samples. It is promising to be developed for application to diagnosis of clinical diseases.
Topics: Antibodies; Antigen-Antibody Reactions; Antigens; Diagnostic Imaging; Humans; Immunoassay; Microspheres; Refractometry
PubMed: 31143781
DOI: 10.1155/2019/5474519