The role of lipids in exosome biology and intercellular communication: Function, analytics and applications.

Exosomes are extracellular vesicles that in recent years have received special attention for their regulatory functions in numerous biological processes. Recent evidence suggests a correlation between the composition of exosomes in body fluids and the progression of some disorders, such as cancer, diabetes and neurodegenerative diseases. In consequence, numerous studies have been performed to evaluate the composition of these vesicles, aiming to develop new biomarkers for diagnosis and to find novel therapeutic targets. On their part, lipids represent one of the most important components of exosomes, with important structural and regulatory functions during exosome biogenesis, release, targeting and cellular uptake. Therefore, exosome lipidomics has emerged as an innovative discipline for the discovery of novel lipid species with biomedical applications. This review summarizes the current knowledge about exosome lipids and their roles in exosome biology and intercellular communication. Furthermore, it presents the state-of-the-art analytical procedures used in exosome lipidomics while emphasizing how this emerging discipline is providing new insights for future applications of exosome lipids in biomedicine.

State-of-the-art exosome loading and functionalization techniques for enhanced therapeutics: a review.

Exosomes are a subpopulation of cell membrane-derived vesicles which play an essential role in cellular communication. In recent years, several studies have exploited the natural properties of exosomes as nanocarriers for several applications such as immunotherapy or drug delivery. Consequently, numerous techniques have been developed to improve their immunogenicity, drug loading efficiency, or targeting. Nonetheless, to date, there is no consensus on which technique results in more advantages for this purpose. In this context, this review discusses the currently used methodologies regarding traditional and engineered exosome loading and targeting techniques. Here, we focus on the advantages and disadvantages of each method while discussing some results obtained in relevant reports. Although there is a lack of evidence regarding the effects of exogenous exosomes in humans and several limitations in exosome isolation and purification techniques at the large-scale exist, the formulation of new exosome-based therapeutics is in the spotlight. Therefore, the development of more efficient functionalization techniques is required to reduce the potential risks associated with the clinical use of these vesicles.

Recent advances and challenges in the recovery and purification of cellular exosomes.

Exosomes are nanovesicles secreted by most cellular types that carry important biochemical compounds throughout the body with different purposes, playing a preponderant role in cellular communication. Because of their structure, physicochemical properties and stability, recent studies are focusing in their use as nanocarriers for different therapeutic compounds for the treatment of different diseases ranging from cancer to Parkinson's disease. However, current bioseparation protocols and methodologies are selected based on the final exosome application or intended use and present both advantages and disadvantages when compared among them. In this context, this review aims to present the most important technologies available for exosome isolation while discussing their advantages and disadvantages and the possibilities of being combined with other strategies. This is critical since the development of novel exosome-based therapeutic strategies will be constrained to the effectiveness and yield of the selected downstream purification methodologies for which a thorough understanding of the available technological resources is needed.

Removal and biotransformation of 4-nonylphenol by Arthrospira maxima and Chlorella vulgaris consortium.

4-Nonylphenol (4-NP) is an anthropogenic contaminant found in different environmental matrices that has an effect over the biotic and abiotic factors within the environment. Bioremediation by microorganisms can be used as a potential treatment to remove this pollutant. In this work, a consortium of two microorganisms, Arthrospira maxima and Chlorella vulgaris, was employed to remove 4-NP from water. The parameters analyzed included cell growth, removal of 4-NP, and 4-NP remnant in the biomass. In addition, the metabolites produced in the process by this consortium were identified. It was found that C. vulgaris is more resistant to 4-NP than A. maxima (cell growth inhibition by 4-NP of 99%). The consortium used in this study had an IC50 greater than any strain of microalgae or cyanobacteria reported for 4-NP removal (9.29 mg/L) and reduced up to 96% of 4-NP in water in the first 48 h of culture. It was also observed that there is a bio-transformation of 4-NP, comparable with the process carried out by another bacterium, in which three similar metabolites were found (4-(1-methyl-octyl)-4-hydroxy-cyclohex-2-enone, 4-nonyl-4-hydroxy-ciclohexa-2,5-dienone and 4-nonyl-4-hydroxy- ciclohex-2-enone) and one that is similar to plant metabolism (4-nonyl-(1-methyl,6,8-metoxy)-hydroxybenzene). These results indicate that microalgae and cyanobacteria consortium can be used to remove 4-NP from water.

Clinical Implications of Exosomal PD-L1 in Cancer Immunotherapy.

Inhibiting the programmed cell death ligand-1 (PD-L1)/programmed cell death receptor-1 (PD-1) signaling axis reinvigorates the antitumor immune response with remarkable clinical efficacy. Yet, low response rates limit the benefits of immunotherapy to a minority of patients. Recent studies have explored the importance of PD-L1 as a transmembrane protein in exosomes and have revealed exosomal PD-L1 as a mechanism of tumor immune escape and immunotherapy resistance. Exosomal PD-L1 suppresses T cell effector function, induces systemic immunosuppression, and transfers functional PD-L1 across the tumor microenvironment (TME). Because of its significant contribution to immune escape, exosomal PD-L1 has been proposed as a biomarker to predict immunotherapy response and to assess therapeutic efficacy. In this review, we summarize the immunological mechanisms of exosomal PD-L1, focusing on the factors that lead to exosome biogenesis and release. Next, we review the effect of exosomal PD-L1 on T cell function and its role across the TME. In addition, we discuss the latest findings on the use of exosomal PD-L1 as a biomarker for cancer immunotherapy. Throughout this review, we propose exosomal PD-L1 as a critical mediator of tumor progression and highlight the clinical implications that follow for immuno-oncology, discussing the potential to target exosomes to advance cancer treatment.

Enhanced exosome-mediated delivery of black bean phytochemicals (Phaseolus vulgaris L.) for cancer treatment applications.

Exosomes are a subpopulation of membrane-derived cellular vesicles (30-150 nm) that play an important role in intercellular communication. Because of their natural function as nanocarriers, several applications have been developed for these nanovesicles, including drug delivery. Here we loaded saponins and flavonoids obtained from a black bean extract (Phaseolus vulgaris L.) with antiproliferative activity into exosomes extracted from different cell lines to induce an enhanced response in vitro. We demonstrated that exosomes can be loaded with at least three different phytochemicals in a one-step process to deliver these compounds to recipient cells. Moreover, we found that the bioactivity of the exosomal extract is greater than those observed in other formulations of the same extract. Our results suggest that exosomes are a promising alternative for improved delivery of complex mixtures of bioactive compounds, such as plant extracts. Therefore, future applications for these nanovesicles may include the development of new products for human use with enhanced nutraceutical properties.