A Comparative Study of Ultrasmall Calcium Carbonate Nanoparticles for Targeting and Imaging Atherosclerotic Plaque.

Atherosclerosis is a complex disease that can lead to life-threatening events, such as myocardial infarction and ischemic stroke. Despite the severity of this disease, diagnosing plaque vulnerability remains challenging due to the lack of effective diagnostic tools. Conventional diagnostic protocols lack specificity and fail to predict the type of atherosclerotic lesion and the risk of plaque rupture. To address this issue, technologies are emerging, such as noninvasive medical imaging of atherosclerotic plaque with customized nanotechnological solutions. Modulating the biological interactions and contrast of nanoparticles in various imaging techniques, including magnetic resonance imaging, is possible through the careful design of their physicochemical properties. However, few examples of comparative studies between nanoparticles targeting different hallmarks of atherosclerosis exist to provide information about the plaque development stage. Our work demonstrates that Gd (III)-doped amorphous calcium carbonate nanoparticles are an effective tool for these comparative studies due to their high magnetic resonance contrast and physicochemical properties. In an animal model of atherosclerosis, we compare the imaging performance of three types of nanoparticles: bare amorphous calcium carbonate and those functionalized with the ligands alendronate (for microcalcification targeting) and trimannose (for inflammation targeting). Our study provides useful insights into ligand-mediated targeted imaging of atherosclerosis through a combination of in vivo imaging, ex vivo tissue analysis, and in vitro targeting experiments.

2 deoxy-D-glucose augments the mitochondrial respiratory chain in heart.

2-Deoxy-D-glucose (2DG) has recently received emergency approval for the treatment of COVID-19 in India, after a successful clinical trial. SARS-CoV-2 infection of cultured cells is accompanied by elevated glycolysis and decreased mitochondrial function, whereas 2DG represses glycolysis and stimulates respiration, and restricts viral replication. While 2DG has pleiotropic effects on cell metabolism in cultured cells it is not known which of these manifests in vivo. On the other hand, it is known that 2DG given continuously can have severe detrimental effects on the rodent heart. Here, we show that the principal effect of an extended, intermittent 2DG treatment on mice is to augment the mitochondrial respiratory chain proteome in the heart; importantly, this occurs without vacuolization, hypertrophy or fibrosis. The increase in the heart respiratory chain proteome suggests an increase in mitochondrial oxidative capacity, which could compensate for the energy deficit caused by the inhibition of glycolysis. Thus, 2DG in the murine heart appears to induce a metabolic configuration that is the opposite of SARS-CoV-2 infected cells, which could explain the compound's ability to restrict the propagation of the virus to the benefit of patients with COVID-19 disease.

Bacterial Nanocellulose and Titania Hybrids: Cytocompatible and Cryopreservable Cell Carriers.

Carrier-assisted cell transplantation offers new strategies to improve the clinical outcomes of cellular therapies. Bacterial nanocellulose (BC) is an emerging biopolymer that might be of great value in the development of animal-free, customizable, and temperature-stable novel cell carriers. Moreover, BC exhibits a myriad of modification possibilities to incorporate additional functionalities. Here, we have synthesized BC-titanium dioxide (TiO2) nanocomposites (BC/TiO2) to evaluate and compare the suitability of not only BC but also a model hybrid nanobiomaterial as cell transplantation supports. This work provides thorough information on the interactions between BC-based substrates and model human cells in terms of cell attachment, morphology, proliferation rate, and metabolic activity. Two methods to partially retrieve the adhered cells are also reported. Both BC and BC/TiO2 substrates are positively evaluated in terms of cytocompatibility and endotoxin content without detecting major differences between BC and BC nanocomposites. Lastly, the effective cryopreservation of cells-BC and cells-BC/TiO2 constructs, yielding high cell viability and intact cell carrier's characteristics after thawing, is demonstrated. Taken together, our results show that both BC and BC/TiO2 enable to integrate the processes of expansion and long-term storage of human cells in transportable, robust and easy to manipulate supports.