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Image correlation analysis has evolved to become a valuable method of analysis of the diffusional motion of molecules in every points of a live cell. Here we compare the iMSD and the 2D-pCF approaches that provide complementary information. The iMSD method provides the law of diffusion and it requires spatial averaging over a small region of the cell. The 2D-pCF does not require spatial averaging and it gives information about obstacles for diffusion at pixel resolution. We show the analysis of the same set of data by the two methods to emphasize that both methods could be needed to have a comprehensive understanding of the molecular diffusional flow in a live cell.

Extracellular vesicles (EVs) are membrane-enclosed bio-nanoparticles secreted by cells and naturally evolved to transport various bioactive molecules between cells and even organisms. These cellular objects are considered one of the most promising bio-nanovehicles for the delivery of native and exogenous molecular cargo. However, many challenges with state-of-the-art EV-based candidates as drug carriers still exist, including issues with scalability, batch-to-batch reproducibility, and cost-sustainability of the final therapeutic formulation. Microalgal extracellular vesicles, which we named nanoalgosomes, are naturally released by various microalgal species. Here, we evaluate the innate biological properties of nanoalgosomes derived from cultures of the marine microalgae Tetraselmis chuii, using an optimized manufacturing protocol. Our investigation of nanoalgosome biocompatibility in preclinical models includes toxicological analyses, using the invertebrate model organism Caenorhabditis elegans, hematological and immunological evaluations ex vivo and in mice. We evaluate nanoalgosome cellular uptake mechanisms in C. elegans at cellular and subcellular levels, and study their biodistribution in mice with accurate space-time resolution. Further examination highlights the antioxidant and anti-inflammatory bioactivities of nanoalgosomes. This holistic approach to nanoalgosome functional characterization demonstrates that they are biocompatible and innate bioactive effectors with unique bone tropism. These findings suggest that nanoalgosomes have significant potential for future therapeutic applications.This study highlights the biocompatibility, tropism, antioxidant and anti-inflammatory properties of nanoalgosomes, extracellular vesicles (EVs) derived from the marine microalga Tetraselmis chuii, suggesting their potential for EV-based therapies. [ABSTRACT FROM AUTHOR]

According to the amyloid hypothesis, in the early phases of Alzheimer's disease (AD), small soluble prefibrillar aggregates of the amyloid β-peptide (Aβ) interact with neuronal membranes, causing neural impairment. Such highly reactive and toxic species form spontaneously and transiently in the amyloid building pathway. A therapeutic strategy consists of the recruitment of these intermediates, thus preventing aberrant interaction with membrane components (lipids and receptors), which in turn may trigger a cascade of cellular disequilibria. Milk α s1 -Casein is an intrinsically disordered protein that is able to inhibit Aβ amyloid aggregation in vitro , by sequestering transient species. In order to test α s1 -Casein as an inhibitor for the treatment of AD, it needs to be delivered in the place of action. Here, we demonstrate the use of large unilamellar vesicles (LUVs) as suitable nanocarriers for α s1 -Casein. Proteo-LUVs were prepared and characterized by different biophysical techniques, such as multiangle light scattering, atomic force imaging, and small-angle X-ray scattering; α s1 -Casein loading was quantified by a fluorescence assay. We demonstrated on a C. elegans AD model the effectiveness of the proposed delivery strategy in vivo . Proteo-LUVs allow efficient administration of the protein, exerting a positive functional readout at very low doses while avoiding the intrinsic toxicity of α s1 -Casein. Proteo-LUVs of α s1 -Casein represent an effective proof of concept for the exploitation of partially disordered proteins as a therapeutic strategy in mild AD conditions.