Aya Al Othman

Metal-organic frameworks (MOFs) are a highly versatile class of ordered porous materials, which hold great promise for different biomedical applications, including antibacterial therapy. In light of the antibacterial effects, these nanomaterials can be attractive for several reasons. First, MOFs exhibit a high loading capacity for numerous antibacterial drugs, including antibiotics, photosensitizers, and/or photothermal molecules. The inherent micro- or meso-porosity of MOF structures enables their use as nanocarriers for simultaneous encapsulation of multiple drugs resulting in a combined therapeutic effect. In addition to being encapsulated into an MOF’s pores, antibacterial agents can sometimes be directly incorporated into an MOF skeleton as organic linkers. Next, MOFs contain coordinated metal ions in their structure. Incorporation of Fe^2/3+, Cu²⁺, Zn²⁺, Co²⁺, and Ag⁺ can significantly increase the innate cytotoxicity of these materials for bacteria and cause a synergistic effect. Finally, abundance of functional groups enables modifying the external surface of MOF particles with stealth coating and ligand moieties for improved drug delivery. To date, there are a number of MOF-based nanomedicines available for the treatment of bacterial infections. This review is focused on biomedical consideration of MOF nano-formulations designed for the therapy of intracellular infections such as Staphylococcus aureus, Mycobacterium tuberculosis, and Chlamydia trachomatis. Increasing knowledge about the ability of MOF nanoparticles to accumulate in a pathogen intracellular niche in the host cells provides an excellent opportunity to use MOF-based nanomedicines for the eradication of persistent infections. Here, we discuss advantages and current limitations of MOFs, their clinical significance, and their prospects for the treatment of the mentioned infections.

Activity-regulated cytoskeleton-associated (Arc) protein is expressed in neural tissue of vertebrates, where it plays a pivotal role in modulation of synaptic communication. In addition, Arc protein forms capsid-like particles, which can encapsulate and transfer mRNA in extracellular vesicles (EVs) between neurons, that could modulate synaptic function and plasticity. Glioma cell networks actively interact with neurons via paracrine signaling and formation of neurogliomal glutamatergic synapses that contribute to cancer cell survival, proliferation, and invasion. Here, we revealed that Arc is expressed in human glioma cell lines, which can produce EVs containing Arc protein and Arc mRNA (or “Arc EVs”). Recombinant Arc protein binds to Arc mRNA with 1.5-fold higher affinity as compared with control mCherry mRNA. Arc EVs from U87 glioma cells internalize and deliver Arc mRNA to recipient U87 cells, where it is translated into a protein. Arc overexpression significantly increases EV production, alters EV morphology, and enhances intercellular transfer of highly expressed mRNA in glioma cell culture. These findings indicate involvement of Arc EVs into mRNA transfer between glioma cells that could contribute to tumor progression and affect synaptic plasticity in cancer patients.