Glycosaminoglycans' for brain health: Harnessing glycosaminoglycan based biomaterials for treating central nervous system diseases and in-vitro modeling.

Dysfunction of the central nervous system (CNS) following traumatic brain injuries (TBI), spinal cord injuries (SCI), or strokes remains challenging to address using existing medications and cell-based therapies. Although therapeutic cell administration, such as stem cells and neuronal progenitor cells (NPCs), have shown promise in regenerative properties, they have failed to provide substantial benefits. However, the development of living cortical tissue engineered grafts, created by encapsulating these cells within an extracellular matrix (ECM) mimetic hydrogel scaffold, presents a promising functional replacement for damaged cortex in cases of stroke, SCI, and TBI. These grafts facilitate neural network repair and regeneration following CNS injuries. Given that natural glycosaminoglycans (GAGs) are a major constituent of the CNS, GAG-based hydrogels hold potential for the next generation of CNS healing therapies and in vitro modeling of CNS diseases. Brain-specific GAGs not only offer structural and biochemical signaling support to encapsulated neural cells but also modulate the inflammatory response in lesioned brain tissue, facilitating host integration and regeneration. This review briefly discusses different roles of GAGs and their related proteoglycan counterparts in healthy and diseases brain and explores current trends and advancements in GAG-based biomaterials for treating CNS injuries and modeling diseases. Additionally, it examines injectable, 3D bioprintable, and conductive GAG-based scaffolds, highlighting their clinical potential for in vitro modeling of patient-specific neural dysfunction and their ability to enhance CNS regeneration and repair following CNS injury in vivo.

Magnetic Resonance Imaging of Tumor-Infiltrating Lymphocytes by Anti-CD3-Conjugated Iron Oxide Nanoparticles.

Immune checkpoint blockade, considered a revolutionary approach in cancer treatment, is only effective in patients with high tumor-infiltrating lymphocytes (TILs). This work aimed to investigate the feasibility of targeted contrast agent (CA) based on dextran-coated superparamagnetic iron oxide nanoparticles (SPIONs-DEX) for TILs detection by magnetic resonance imaging (MRI) studies. To do so, we synthesized an MRI CA by conjugating SPIONs-DEX to an anti-CD3 monoclonal antibody via cyanogen bromide as a cross-linker. In vitro assessments demonstrated the higher labeling efficiency of the developed CA to CD3+ lymphocytes compared to SPIONs-DEX. In vivo MRI of a xenograft model of CD3+ lymphocytes revealed the significant signal loss after the intravenous injection of the bioconjugate by ∼34 % and 21 % in T2 *-weighted and T2 -weighted images, respectively. The histopathological evaluation of xenograft tumors confirmed the labeling of lymphocytes by the targeted CA. This approach could open up a new horizon in the non-invasive assessment of TILs to identify patients eligible for immunotherapy.

Bio-conjugation of anti-human CD3 monoclonal antibodies to magnetic nanoparticles by using cyanogen bromide: A potential for cell sorting and noninvasive diagnosis.

The conjugation of monoclonal antibodies with superparamagnetic iron oxide nanoparticles (SPIONs) has appeared as a potential multifunctional clinical tool, which can effectively diagnose cancers and monitor their treatment, specifically. Despite the presence of different methods for conjugating antibodies to iron oxide nanoparticles, novel cost-effective and simpler conjugation techniques should be performed in this regard. In current study, an anti-CD3 monoclonal antibody was conjugated to the Fe3O4 coated by carboxymethyl dextran (CMD) using cyanogen bromide (CNBr). Moreover, EDC/NHS techniques were applied as a positive control. The experimental results showed that the Conjugation was performed and the presence of the antibody conjugated to the MNPs in human xenograft tumors was confirmed using Prussian blue (PB) staining, following magnetic resonance imaging (MRI), 30 min after injection. This conjugation method was shown to be able to separate CD3+ T lymphocytes efficiently from whole blood with high purity. Accordingly, this type of bio-conjugation method can be utilized in the future for cell sorting, and can be applied for adopted cell therapies such as CAR-T cell (Chimeric antigen receptor T cell) therapy, as well as targeted MRI imaging.

Green synthesis of silver nanoparticles using Zingiber officinale and Thymus vulgaris extracts: characterisation, cell cytotoxicity, and its antifungal activity against Candida albicans in comparison to fluconazole.

Fluconazole (FLZ) application as a highly successful commercial antifungal azole agent to treat the fungal infections is limited due to emergence of FLZ-resistant candida. In this study, the potential of green synthesised silver nanoparticles (NPs) as an antifungal agent against Candida albicans fungal pathogen is investigated. The extract of ginger (Zingiber officinale) and thyme (Thymus vulgaris) plays as reducing agent, capping agent and antifungal agent. The UV-visible spectroscopy shows the peak of surface plasmon resonance of synthesised Ag NPs after a period of time. The synthesised Ag NPs are spherical, with average sizes of 12 and 18 nm based on ginger and thyme extract, respectively. Fourier transform infrared spectroscopy confirms the adsorption of the plant extract on the surface of the as-prepared Ag NPs. Based on the minimum inhibitory concentration (MIC) method against Candida albicans, the antifungal activity of as-prepared green synthesised Ag NPs shows higher inhibitory in comparison to FLZ. Finally, the Ag NPs synthesised via thyme extract shows no cytotoxicity with concentration below 3.5 ppm, which can be considered as an appropriate candidate instead of FLZ to treat the superficial fungal infections.