Welcome to Laboratory of Nano-Bio Interactions! The lab primary research goals are directed toward overcoming (nano)biotechnology issues for early detection and better treatment of the catastrophic diseases. The five most important research projects are summarized below:
1- Understanding protein corona implications at interfaces of nanoparticles and biological fluids(e.g. human plasma)
Due to their increasing potential applications in diagnosis and treatment of diverse diseases types, nanoparticles (NPs) have attracted the growing attention in various branches of medical sciences. Owing to the potential risks to human health together with environmental issues, however, there are increasing concerns about safe design of NPs. Therefore, we need to have a full understanding of all the major interactions that occur at the nano-bio interfaces to design safe, reliable, and high-yield NPs, for desired biomedical purposes. To that end, extensive studies have been undertaken to probe every individual crucial factor that should be considered at the nano-bio interfaces. However, to date, the results have been disappointing there have been too many conflicting findings or cytotoxicity and biological fate while using the exact same NPs. This suggests that there are still too many "overlooked" factors at nanoparticle-biological complex medium. Over the last few years, a considerable amount of research has been being performed to seek out these hidden factors. Since 2008, the main goal of the BioSPION laboratory, together with our collaborative centers from different prestigious universities, including Stanford University and University of Illinois at Urbana Champaign, has been being dedicated to seek and introduce these factors (e.g., effect of nanoparticles on environmental health, concept of Personalized Protein Corona and immune response, through cytokine secretion, to the disease-specific corona decorated nanoparticles) to the scientific community.
2- Fabrication of novel nanoparticles against antibacterial resistance issues
The combination of patients with poor immune systems, prolonged exposure to anti-infective drugs, and cross-infections has given rise to nosocomial infections with highly resistant pathogens, a growing threat called “antibiotic resistance”. We performed extensive research on preparation of different types of engineered multimodal NPs, that are completely compatible with the cells. These NPs were comprised of a magnetic core and a silver ring with a ligand gap and resulted in high-yield antibacterial effects and eradication of bacterial biofilms.
3- Design of the smart cell imprinted smart nano-patterned substrates for controlling stem cell differentiation toward cardiomyocytes, chondrocytes, and keratinocytes
Stem cells have enormous potential therapeutic effects in catastrophic diseases such as cancer and neurodegenerative diseases. To realize that potential, controlling of the behavior of stem cells cultured in the laboratory is a crucial issue. Growth factors have been used as a conventional method for the control of stem cell fate. However, disappointing clinical results with some of the growth factors (e.g., angiogenic factors) demonstrated the emerging need for the development of alternative strategies to induce stem cells differentiation. It is now recognized that stem cells can sense and produce an appropriate response to the physicochemical properties (e.g., surface composition, surface adhesive ligands and their local densities, surface topography, surface smoothness/roughness, and surface flexibility/rigidity) of their extracellular matrix (ECM) via the regulation of their complex signaling pathways. By activation of these specific signaling pathways, stem cells can control their critical future function, such as their gene expression profile and differentiation. In addition to substrate stiffness, it has been also shown that the substrate pattern can affect the response of stem cells. In this case, substrates with various micro- and nanotopographies have been intensively used to control the differentiations of stem cells. Motivated by previous reports, my lab made a potentially reliable, reproducible, and cheap method for controlling the fate of stem cells by using both micro- and nano-patterned substrates that biomimic cell shapes. Patterns are obtained by employing cells as a template on which a silicone mold was cast, leaving the cells’ topography imprinted on the cured substrates. Thus, substrates resemble the specific topography of the cellular plasma membranes of the cells which had been used as a template and consequently may emulate the surface of cells. These substrates proved great capability to differentiate mesenchymal stem cells into chondrocytes, and keratinocytes. Currently, we are working on the new types of substrates to prepare mature cardiomyocytes for cardiac regeneration.
4- Biomaterials for Cardiac Regeneration
We are actively working on the biomaterials which aims to develop and optimize a novel cardiovascular patch system engineered to disrupt the pathological remodeling that follows acute heart injuries and promote cardiac regeneration. The patch consists of a dense collagen scaffold, with optimized biomechanical properties approaching those of embryonic epicardium. Our obtained preliminary data indicate that application of our patch laden with epicardial paracrine factors protected the mouse heart against infarct at the anatomical and functional levels. The ultimate goal of this research is to set up a novel platform for treating acute heart injuries through application of exogenous biomimetic scaffolds containing epicardial cardiogenic macromolecules.
5- Probing overlooked factors in Alzheimer’s DiseaseSince last 5 year, we have been actively working on the possible strategies to enhance the therapeutic approaches for controlling Alzheimer's disease (AD). Two decades of the amyloid-β (Aβ) hypothesis in AD and the prominence of Aβ-targeting strategies have yet to meet the levels of original expectation. We probed the effects of various NPs with different surface decoration (from synthetic to proteins) on the Aβ fibrillation process. Beside using nanobiomaterials to control the fibrillation process, we also explored several ignored factors in the progress of AD. Disappointing results in numerous Phase II/III studies have called for are-examination of the validity of the Aβ-targeting approaches as an intervention strategy in AD. We proposed that the mid-life onset of chronic conditions (e.g., hypertension, diabetes, insulin intolerance, and depression nominated as risk factors for the later development of AD) points to the possibility that each condition could involve mechanisms, which while relatively modest over a short-term, could have significant accumulative effects. What may also not be fully appreciated is that a number of these conditions involve potential disturbances to multivalent cations (MC) levels through various mechanisms such as autophagy, oxidative stress, and apoptosis. Furthermore, some MCs have intimate associations with the mechanisms by which Aβ pathology manifests. Considering various lines of evidence and incorporating statistical analysis on Disability–Adjusted Life Years (DALYs) data of both causes of and prevalence of multifactorial risk factors in different world regions, we proposed an MC hypothesis for AD. More specifically, we found that MC imbalance marks many chronic conditions and because of their involvement with Aβ pathology, could reflect that Aβmay be a vital manifestation and marker of underlying MC imbalance. Thus, careful targeting of MC imbalance may provide an alternative or complementary interventional approach to current Aβ treatment strategies. Based on our overall finding in AD, we plan to prepare an optoelectronic nose for fast detection of AD at the very early stage.
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