Advances in Alzheimer's Diagnosis and Therapy: The Implications of Nanotechnology

Alzheimer's disease (AD) is a type of dementia that causes major issues for patients’ memory, thinking, and behavior. Despite efforts to advance AD diagnostic and therapeutic tools, AD remains incurable due to its complex and multifactorial nature and lack of effective diagnostics/therapeutics. Nanoparticles (NPs) have demonstrated the potential to overcome the challenges and limitations associated with traditional diagnostics/therapeutics. Nanotechnology is now offering new tools and insights to advance our understanding of AD and eventually may offer new hope to AD patients. Here, we review the key roles of nanotechnologies in the recent literature, in both diagnostic and therapeutic aspects of AD, and discuss how these achievements may improve patient prognosis and quality of life. Nanotechnology offers a multitude of diagnostic, mechanistic, and therapeutic tools for Alzheimer's disease (AD). Nanobased approaches are already providing new insights to address the pathogenesis of AD. Nanotechnology addresses the multifaceted nature of age-related degeneration, while simplistic linear models of AD, such as amyloid cascade, have failed to address it. Nanoparticles have the utility to address each compartment and phase of the disease in a highly sophisticated manner. Nanotechnology offers new hope for AD where conventional approaches have stalled

Cell-Imprinted Substrates Direct the Fate of Stem Cells

Smart nanoenvironments were obtained by cell-imprinted substrates based on mature and dedifferentiated chondrocytes as templates. Rabbit adipose derived mesenchymal stem cells (ADSCs) seeded on these cell-imprinted substrates were driven to adopt the specific shape (as determined in terms of cell morphology) and molecular characteristics (as determined in terms of gene expression) of the cell types which had been used as template for the cell-imprinting. This method might pave the way for a reliable, efficient, and cheap way of controlling stem cell differentiation. Data also suggest that besides residual cellular fragments, which are presented on the template surface, the imprinted topography of the templates plays a role in the differentiation of the stem cells

Engineering of Mature Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Using Substrates with Multiscale Topography

Producing mature and functional cardiomyocytes (CMs) by in vitro differentiation of induced pluripotent stem cells (iPSCs) using only biochemical cues is challenging. To mimic the biophysical and biomechanical complexity of the native in vivo environment during the differentiation and maturation process, polydimethylsiloxane substrates with 3D topography at the micrometer and sub-micrometer levels are developed and used as cell-culture substrates. The results show that while cylindrical patterns on the substrates resembling mature CMs enhance the maturation of iPSC-derived CMs, sub-micrometer-level topographical features derived by imprinting primary human CMs further accelerate both the differentiation and maturation processes. The resulting CMs exhibit a more-mature phenotype than control groups—as confirmed by quantitative polymerase chain reaction, flow cytometry, and the magnitude of beating signals—and possess the shape and orientation of mature CMs in human myocardium—as revealed by fluorescence microscopy, Ca2+ flow direction, and mitochondrial distribution. The experiments, combined with a virtual cell model, show that the physico-mechanical cues generated by these 3D-patterned substrates improve the phenotype of the CMs via the reorganization of the cytoskeletal network and the regulation of chromatin conformation

Sensing of Alzheimer's Disease and Multiple Sclerosis Using Nano-Bio Interfaces.

Abstract A simple and green method for the determination of cyanide ions (CN-) has been developed which is based on copper nanoparticles (CuNPs) acting as a fluorescent probe in aqueous solutions. In this study, fluorescent CuNPs have been synthesized in the presence of ascorbic acid which acts both as a reducing and protecting agent. The preparation of CuNPs by this method is very simple, low cost, high yield, and reproducible. The prepared CuNPs have the small average diameter of 10nm and show a blue emission at 440nm. However, upon the addition of CN- into the CuNPs sensing system, its fluorescence was quenched considerably as a result of the strong interaction between cyanide and copper. Under optimized conditions, a good relationship was observed between the fluorescence quenching of the system and the concentration of CN- in the range of 0.5-18µmolL-1 with a detection limit of 0.37µmolL-1. In addition, the developed sensor has a high selectivity and simple operations. Furthermore, as a cost-effective and selective fluorescent probe, the CuNPs sensor was successfully employed for the detection of CN- ions in water samples

Effect of Cell Sex on Uptake of Nanoparticles: The Overlooked Factor at the Nanobio Interface

Cellular uptake of nanoparticles (NPs) depends on the nature of the <i>nanobio</i> system including the solid <i>nano</i>components (<i>e</i>.<i>g</i>., physicochemical properties of NPs), <i>nanobio interfaces</i> (<i>e</i>.<i>g</i>., protein corona composition), and the <i>cellular characteristics</i> (<i>e</i>.<i>g</i>., cell type). In this study, we document the role of sex in cellular uptake of NPs as an “overlooked” factor in nanobio interface investigations. We demonstrate that cell sex leads to differences in NP uptake between male and female human amniotic stem cells (hAMSCs), with greater uptake by female cells. hAMSCs are one of the earliest sources of somatic stem cells. The experiments were replicated with primary fibroblasts isolated from the salivary gland of adult male and female donors of similar ages, and again the extent of NP uptake was altered by cell sex. However, in contrast to hAMSCs, uptake was greater in male cells. We also found out that female <i>versus</i> male amniotic stem cells exhibited different responses to reprogramming into induced pluripotent stem cells (iPSCs) by the Yamanaka factors. Thus, future studies should consider the effect of sex on the nanobio interactions to optimize clinical translation of NPs and iPSC biology and to help researchers to better design and produce safe and efficient therapeutic <i>sex-specific</i> NPs