Farbod Ghobadinezhad

Autoimmune disease, caused by unwanted immune responses to self-antigens, affects millions of people each year and poses a great social and economic burden to individuals and communities. In the course of autoimmune disorders, including rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes mellitus, and multiple sclerosis, disturbances in the balance between the immune response against harmful agents and tolerance towards self-antigens lead to an immune response against self-tissues. In recent years, various regulatory immune cells have been identified. Disruptions in the quality, quantity, and function of these cells have been implicated in autoimmune disease development. Therefore, targeting or engineering these cells is a promising therapeutic for different autoimmune diseases. Regulatory T cells, regulatory B cells, regulatory dendritic cells, myeloid suppressor cells, and some subsets of innate lymphoid cells are arising as important players among this class of cells. Here, we review the roles of each suppressive cell type in the immune system during homeostasis and in the development of autoimmunity. Moreover, we discuss the current and future therapeutic potential of each one of these cell types for autoimmune diseases.

Cancer is one of the most common diseases and causes of death worldwide. Since common treatment approaches do not yield acceptable results in many patients, developing innovative strategies for effective treatment is necessary. Immunotherapy is one of the promising approaches that has been highly regarded for preventing tumor recurrence and new metastases. Meanwhile, inhibiting immune checkpoints is one of the most attractive methods of cancer immunotherapy. Cytotoxic T lymphocyte-associated protein-4 (CTLA-4) is an essential immune molecule that plays a vital role in cell cycle modulation, regulation of T cell proliferation, and cytokine production. This molecule is classically expressed by stimulated T cells. Inhibition of overexpression of immune checkpoints such as CTLA-4 receptors has been confirmed as an effective strategy. In cancer immunotherapy, immune checkpoint-blocking drugs can be enhanced with nanobodies that target immune checkpoint molecules. Nanobodies are derived from the variable domain of heavy antibody chains. These small protein fragments have evolved entirely without a light chain and can be used as a powerful tool in imaging and treating diseases with their unique structure. They have a low molecular weight, which makes them smaller than conventional antibodies while still being able to bind to specific antigens. In addition to low molecular weight, specific binding to targets, resistance to temperature, pH, and enzymes, high ability to penetrate tumor tissues, and low toxicity make nanobodies an ideal approach to overcome the disadvantages of monoclonal antibody-based immunotherapy. In this article, while reviewing the cellular and molecular functions of CTLA-4, the structure and mechanisms of nanobodies' activity, and their delivery methods, we will explain the advantages and challenges of using nanobodies, emphasizing immunotherapy treatments based on anti-CTLA-4 nanobodies.

The blood-brain barrier (BBB) is considered as the most challenging barrier in brain drug delivery. Indeed, there is a definite link between the BBB integrity defects and central nervous systems (CNS) disorders, such as neurodegenerative diseases and brain cancers, increasing concerns in the contemporary era because of the inability of most therapeutic approaches. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have already been identified as having several advantages in facilitating the transportation of hydrophilic and hydrophobic agents across the BBB. This review first explains BBB functions and its challenges in brain drug delivery, followed by a brief description of nanoparticle-based drug delivery for brain diseases. A detailed presentation of recent progressions in optimizing SLNs and NLCs for controlled release drug delivery, gene therapy, targeted drug delivery, and diagnosis of neurodegenerative diseases and brain cancers is approached. Finally, the problems, challenges, and future perspectives in optimizing these carriers for potential clinical application were described briefly.

Despite many advances in cancer treatment, cancer still remains a major global health problem owing to its high rate of recurrence, the tendency to metastasize, and the development of drug resistance. In addition to animal models, cancer researchers can employ in vitro tumor models to mimic in vivo tumor microenvironment with the purpose of discovering new therapeutic approaches. In order to engineer a realistic tumor microenvironment that can recapitulate not only cancer progression but also angiogenesis and metastasis, many complex interacting factors must be taken into account. Strategies based on 3D bioprinting are now being investigated, which could simulate the tumor microenvironment by bioprinting living human cells. These approaches allow the accurate placement of the normal cancer cells and bioactive macromolecules to monitor cancer progression, facilitate drug screening, and provide to design new generations of anticancer therapies. The present review summarizes progress in the area of 3D bioprinting utility for mimicking the tumor microenvironment, and studying the physicochemical/biological factors for new and improved therapeutic and diagnostic applications.