Justfreeman0075

The tumor microenvironment (TME) plays a central role in regulating antitumor immune responses. As an important part of the TME, alternatively activated type 2 (M2) macrophages drive the development of primary and secondary tumors by promoting tumor cell proliferation, tumor angiogenesis, extracellular matrix remodeling and overall immunosuppression. Immunotherapy approaches targeting tumor-associated macrophages (TAMs) in order to reduce the immunosuppressive state in the TME have received great attention. Although these methods hold great potential for the treatment of several cancers, they also face some limitations, such as the fast degradation rate of drugs and drug-induced cytotoxicity of organs and tissues. Nanomedicine formulations that prevent TAM signaling and recruitment to the TME or deplete M2 TAMs to reduce tumor growth and metastasis represent encouraging novel strategies in cancer therapy. They allow the specific delivery of antitumor drugs to the tumor area, thereby reducing side effects associated with systemic application. In this review, we give an overview of TAM biology and the current state of nanomedicines that target M2 macrophages in the course of cancer immunotherapy, with a specific focus on nanoparticles (NPs). We summarize how different types of NPs target M2 TAMs, and how the physicochemical properties of NPs (size, shape, charge and targeting ligands) influence NP uptake by TAMs in vitro and in vivo in the TME. Furthermore, we provide a comparative analysis of passive and active NP-based TAM-targeting strategies and discuss their therapeutic potential.Autoimmune diseases such as rheumatoid arthritis are caused by immune system recognition of self-proteins and subsequent production of effector T cells that recognize and attack healthy tissue. Therapies for these diseases typically utilize broad immune suppression, which can be effective, but which also come with an elevated risk of susceptibility to infection and cancer. learn more T cell recognition of antigens is driven by binding of T cell receptors to peptides displayed on major histocompatibility complex proteins (MHCs) on the cell surface of antigen-presenting cells. Technology for recombinant production of the extracellular domains of MHC proteins and loading with peptides to produce pMHCs has provided reagents for detection of T cell populations, and with the potential for therapeutic intervention. However, production of pMHCs in large quantities remains a challenge and a translational path needs to be established. Here, we demonstrate a fusion protein strategy enabling large-scale production of pMHCs. A peptide corresponding to amino acids 259-273 of collagen II was fused to the N-terminus of the MHC_II beta chain, and the alpha and beta chains were each fused to human IgG4 Fc domains and co-expressed. A tag was incorporated to enable site-specific conjugation. The cytotoxic drug payload, MMAF, was conjugated to the pMHC and potent, peptide-specific killing of T cells that recognize the collagen pMHC was demonstrated with tetramerized pMHC-MMAF conjugates. Finally, these pMHCs were incorporated into MMAF-loaded 3DNA nanomaterials in order to provide a biocompatible platform. Loading and pMHC density were optimized, and peptide-specific T cell killing was demonstrated. These experiments highlight the potential of a pMHC fusion protein-targeted, drug-loaded nanomaterial approach for selective delivery of therapeutics to disease-relevant T cells and new treatment options for autoimmune disease.Cancer immunotherapies have been approved as standard second-line or in some cases even as first-line treatment for a wide range of cancers. However, immunotherapy has not shown clinically relevant success in glioblastoma (GBM). This is principally due to the brain's "immune-privileged" status and the peculiar tumor microenvironment (TME) of GBM characterized by a lack of tumor-infiltrating lymphocytes and the establishment of immunosuppressive mechanisms. Herein, we explore a local mild thermal treatment, generated via cubic-shaped iron oxide magnetic nanoparticles (size ~17 nm) when exposed to an external alternating magnetic field (AMF), to induce immunogenic cell death (ICD) in U87 glioblastoma cells. In accordance with what has been observed with other tumor types, we found that mild magnetic hyperthermia (MHT) modulates the immunological profile of U87 glioblastoma cells by inducing stress-associated signals leading to enhanced phagocytosis and killing of U87 cells by macrophages. At the same time, we demonstrated that mild magnetic hyperthermia on U87 cells has a modulatory effect on the expression of inhibitory and activating NK cell ligands. Interestingly, this alteration in the expression of NK ligands in U87 cells upon MHT treatment increased their susceptibility to NK cell killing and enhanced NK cell functionality. The overall findings demonstrate that mild MHT stimulates ICD and sensitizes GBM cells to NK-mediated killing by inducing the upregulation of specific stress ligands, providing a novel immunotherapeutic approach for GBM treatment, with potential to synergize with existing NK cell-based therapies thus improving their therapeutic outcomes.

Bile acid-based drug encapsulation for oral delivery has been recently explored in our laboratory and has shown to be beneficial in terms of drug-targeted delivery and release profile, but stability at various temperatures has not previously been examined; hence, this is the aim of this study.

Various types of bile acid-based microcapsules containing the drug metformin were produced and tested for accelerated temperature-controlled profiles, as well as morphology, elemental composition, drug content, resilience, floatability, wettability and release profiles at various pH values.

Accelerated temperature-controlled analysis showed negligible effects on morphology, size, or shape at very low temperatures (below 0 °C), while higher temperatures (above 25 °C) caused alterations. Drug contents, morphology and elemental composition remained similar, while wettability and the release profiles showed formulation-dependent effects.

Results suggest that bile acid-based microcapsules containing metformin are affected by temperature; hence, their shelf life is likely to be affected by storage temperature, all of which have a direct impact on drug release and stability profiles.

Results suggest that bile acid-based microcapsules containing metformin are affected by temperature; hence, their shelf life is likely to be affected by storage temperature, all of which have a direct impact on drug release and stability profiles.Wound dressings have become a crucial treatment for wound healing due to their convenience, low cost, and prolonged wound management. As cutting-edge biomaterials, marine polysaccharides are divided from most marine organisms. It possesses various bioactivities, which allowing them to be processed into various forms of wound dressings. Therefore, a comprehensive understanding of the application of marine polysaccharides in wound dressings is particularly important for the studies of wound therapy. In this review, we first introduce the wound healing process and describe the characteristics of modern commonly used dressings. Then, the properties of various marine polysaccharides and their application in wound dressing development are outlined. Finally, strategies for developing and enhancing marine polysaccharide wound dressings are described, and an outlook of these dressings is given. The diverse bioactivities of marine polysaccharides including antibacterial, anti-inflammatory, haemostatic properties, etc., providing excellent wound management and accelerate wound healing. Meanwhile, these biomaterials have higher biocompatibility and biodegradability compared to synthetic ones. On the other hand, marine polysaccharides can be combined with copolymers and active substances to prepare various forms of dressings. Among them, emerging types of dressings such as nanofibers, smart hydrogels and injectable hydrogels are at the research frontier of their development. Therefore, marine polysaccharides are essential materials in wound dressings fabrication and have a promising future.The present study describes the use of two taste-masking polymers to fabricate a formulation of chlorpheniramine maleate for paediatric administration. Co-axial electrospinning was utilized to create layered nanofibres; the two polymers, Eudragit® E PO and Kollicoat® Smartseal, were alternated between the core and the shell of the system in order to identify the optimum taste-masked formulation. The drug was loaded in the core on all occasions. It was found that the formulation with Kollicoat® Smartseal in the core with the drug, and Eudragit® E PO in the shell showed the most effective taste-masking compared to the other formulations. These fibres were in the nano-range and had smooth morphology as verified by scanning electron microscopy. Solid-state characterization and thermal analysis confirmed that amorphous solid dispersions were formed upon electrospinning. The Insent E-tongue was used to assess the taste-masking efficiency of the samples, and it was found that this formulation was undetectable by the bitter sensor, indicating successful taste-masking compared to the raw version of the drug. The E-tongue also confirmed the drug's bitterness threshold as compared to quinine HCl dihydrate, a parameter that is useful for formulation design and taste-masking planning.The freezing phenomenon has a dramatic impact on the quality of freeze-dried products. Several freezing models applied to solutions in vials have been proposed to predict the resulting product morphology and describe heat transfer mechanisms. However, there is a lack of detailed experimental observations of the freezing phenomenon in vials in the literature. Thus, the present work offers new experimental observations of the freezing phenomenon in vials by infrared (IR) thermography. IR imaging allowed each vial's whole axial temperature profile to be collected during freezing, providing significant insights into the process. Spontaneous nucleation and vacuum-induced surface freezing (VISF), as a controlled nucleation technique, are investigated. Batches having vials in direct contact with the shelf (exchanging heat mainly through conduction) as well as suspended (exchanging heat mainly through natural convection and radiation) were tested. The study used three solutions sucrose 5%, mannitol 5%, and dextran 10%. SEM images coupled with an automated image segmentation technique were also performed to examine possible correlations between the freezing observations and the resulting pore size distributions. IR thermography was found to be a promising tool for experimentally predicting the resulting product morphology in-line.Diagnostic imaging of aggressive cancer with a high stroma content may benefit from the use of imaging contrast agents targeted with peptides that have high binding affinity to the extracellular matrix (ECM). In this study, we report the use of superparamagnetic iron-oxide nanoparticles (IO-NP) conjugated to a nonapeptide, CSGRRSSKC (CSG), which specifically binds to the laminin-nidogen-1 complex in tumours. We show that CSG-IO-NP accumulate in tumours, predominantly in the tumour ECM, following intravenous injection into a murine model of pancreatic neuroendocrine tumour (PNET). In contrast, a control untargeted IO-NP consistently show poor tumour uptake, and IO-NP conjugated to a pentapeptide. CREKA that bind fibrin clots in blood vessels show restricted uptake in the angiogenic vessels of the tumours. CSG-IO-NP show three-fold higher intratumoral accumulation compared to CREKA-IO-NP. Magnetic resonance imaging (MRI) T2-weighted scans and T2 relaxation times indicate significant uptake of CSG-IO-NP irrespective of tumour size, whereas the uptake of CREKA-IO-NP is only consistent in small tumours of less than 3 mm in diameter.