Vitamin B12 (VitB12) is a naturally occurring compound produced by microorganisms and an essential nutrient for humans. Several papers highlight the role of VitB12 deficiency in bone and heart health, depression, memory performance, fertility, embryo development, and cancer, while VitB12 treatment is crucial for survival in inborn errors of VitB12 metabolism. VitB12 is administrated through intramuscular injection, thus impacting the patients’ lifestyle, although it is known that oral administration may meet the specific requirement even in the case of malabsorption. Furthermore, the high-dose injection of VitB12 does not ensure a constant dosage, while the oral route allows only 1.2% of the vitamin to be absorbed in human beings. Nanocarriers are promising nanotechnology that can enable therapies to be improved, reducing side effects. Today, nanocarrier strategies applied at VitB12 delivery are at the initial phase and aim to simplify administration, reduce costs, improve pharmacokinetics, and ameliorate the quality of patients’ lives. The safety of nanotechnologies is still under investigation and few treatments involving nanocarriers have been approved, so far. Here, we highlight the role of VitB12 in human metabolism and diseases, and the issues linked to its molecule properties, and discuss how nanocarriers can improve the therapy and supplementation of the vitamin and reduce possible side effects and limits.
Extracellular vesicles (EVs) are membranous nanoparticles secreted by almost all cell types. Reflecting the physiopathological state of the parental cell, EVs circulate in all body fluids, reaching distant cell targets and delivering different bioactive cargoes. As biological carriers, EVs influence their microenvironment altering cellular responses, being considered promising biomarkers for both physiological and pathological conditions. EVs are heterogeneous in terms of size and composition, depending on cell type and exposure to stimuli, and different methods have been developed to characterize their morphological, biophysical, and biochemical features. Among them, electron microscopy (EM) is the main technique used, however, the lack of standardized protocols makes it difficult to characterize EVs with a good reproducibility, thus using multiple approaches may represent a way to obtain more precise information. Furthermore, the relationship between architecture and function, not only in a molecular, but also in a cellular level, is gaining growing emphasis, characterizing morphometric parameters may represent a distinct, but effective approach to study the physiopathological state of the cell. Atomic force microscopy (AFM), may represent a promising method to study in detail EVs dynamics throughout the cell surface and its variations related to the physiological state, overcoming the limits of EM, and providing more reliable information. In this study, human neuroblastoma SH-SY5Y cell line, a cellular model to investigate neurodegeneration and oxidative stress, has been used to perform a comparative morphological and quantitative analysis of membrane budding and isolated large vesicles-enriched (microvesicles-like vesicles; MVs) fraction from control or oxidative stressed cells. Our main goal was to build up a methodology to characterize EVs morphology and spatial distribution over the cell surface in different physiological conditions, and to evaluate the efficacy of AFM against conventional EM. Interestingly, both microscopy techniques were effective for this analysis, but AFM allowed to reveal a differential profiling of plasma membrane budding between the physiological and the stress condition, indicating a potential relationship between mechanical characteristics and functional role. The results obtained may provide interesting perspectives for the use of AFM to study EVs, validating a morphometric approach to understand the pathophysiological state of the cell related to EVs trafficking.
Extracellular vesicles (EVs) are widely recognized as intercellular communication mediators. Among the different biological processes, EVs play a role in viral infections, supporting virus entrance and spread into host cells and immune response evasion. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection became an urgent public health issue with significant morbidity and mortality worldwide, being responsible for the current COVID-19 pandemic. Since EVs are implicated in SARS-CoV-2 infection in a morphological and functional level, they have gained growing interest for a better understanding of SARS-CoV-2 pathogenesis and represent possible diagnostic tools to track the disease progression. Furthermore, thanks to their biocompatibility and efficient immune activation, the use of EVs may also represent a promising strategy for the development of new therapeutic strategies against COVID-19. In this review, we explore the role of EVs in viral infections with a focus on SARS-CoV-2 biology and pathogenesis, considering recent morphometric studies. The common biogenesis aspects and structural similarities between EVs and SARS-CoV-2 will be examined, offering a panoramic of their multifaceted interplay and presenting EVs as a machinery supporting the viral cycle. On the other hand, EVs may be exploited as early diagnostic biomarkers and efficient carriers for drug delivery and vaccination, and ongoing studies will be reviewed to highlight EVs as potential alternative therapeutic strategies against SARS-CoV-2 infection.
Hepatic fibrosis (HF) is a major cause of liver-related disorders and together with cancer-associated fibroblasts can favor liver cancer development by modulating the tumor microenvironment. Advanced HF, characterized by an excess of extracellular matrix (ECM), is mediated by TGF- β1, that activates hepatic stellate cells (HSCs) and fibroblasts. A TGF-β1 receptor inhibitor, LY2157299 or Galunisertib (GLY), has shown promising results against chronic liver progression in animal models, and we show that it can be further improved by enhancing GLYs bioavailability through encapsulation in polymeric polygalacturonic-polyacrylic acid nanomicelles (GLY-NMs). GLY-NMs reduced HF in an in vivo rat model of liver fibrosis induced by intraperitoneal injection of CCl4 as shown by the morphological, biochemical, and molecular biology parameters of normal and fibrotic livers . Moreover, GLY-NM was able to induce recovery from HF better than free GLY. Indeed, the encapsulated drug reduces collagen deposition, hepatic stellate cells (HSCs) activation, prevents fatty degeneration and restores the correct lobular architecture of the liver as well as normalizes the serum parameters and expression of the genes involved in the onset of HF. In summary, GLY-NM improved the pharmacological activity of the free TGF- β1 inhibitor in the in vivo HF treatment and thus is a candidate as a novel therapeutic strategy.
Extracellular vesicles (EVs) are important mediators of intercellular communication in several physiopathological conditions. Oxidative stress alters EVs release and cargo composition depending on the cell type and stimulus. Recently, most of the EVs studies have focused on the characterization of their cargo, rather than on the morphological features (i.e., size distribution, shape, and localization on the cell surface). Due to their high heterogeneity, to fully characterize EVs both the functional and morphological characterization are required. Atomic force microscopy (AFM), introduced for cell morphological studies at the nanoscale, represents a promising method to characterize in detail EVs morphology, dynamics along the cell surface, and its variations reflecting the cell physiological status. In the present study, untreated or H2O2-treated wild-type and SOD1-G93A SH-SY5Y cells have been compared performing a transmission electron microscopy (TEM) and AFM morpho-quantitative analysis of budding and released vesicles. Intriguingly, our analysis revealed a differential EVs profiling, with an opposite behavior and implying different cell areas between WT and SOD1-G93A cells, on both physiological conditions and after H2O2 exposure. Our results empower the relationship between the morphological features and functional role, further proving the efficacy of EM/AFM in giving an overview of the cell physiology related to EVs trafficking.
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