Harnessing Nature’s nanoSecrets: biocompatibility, biodistribution and bioactivity of extracellular vesicles derived from microalgae

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Abstract

Nanoalgosomes are extracellular vesicles (EVs) released by microalgal cells that can mediate intercellular and cross-kingdom communication. In the present study, starting from the optimized nanoalgosome manufacturing from cultures of marine microalgae, we evaluated their innate biological properties in preclinical models. Our investigation of nanoalgosome biocompatibility included toxicological analyses, starting from studies on the invertebrate model organism Caenorhabditis elegans, proceeding to hematological and immunological evaluations in mice and immune-compatibility ex vivo . Nanoalgosome biodistribution was evaluated in mice with accurate space-time resolution, and in C. elegans at cellular and subcellular levels. Further examination highlighted the antioxidant and anti-inflammatory bioactivities of nanoalgosomes. This holistic approach to nanoalgosome functional characterization showcases that nanoalgosomes are innate effectors and potential drug delivery system for novel cosmetic formulations and EV-based therapies.

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  1. Thereafter, we decided to use the concentration of 20 µg/mL to further evaluate nanoalgosome effects on animal fitness45.

    Thank you for running this experiment and reporting the concentration gradient! I was a bit confused why 20 ug/ml was selected for the worms in the last paragraph until reading this. Thank you for making it clear!

  2. 2 µg/mL

    Is this the same concentration of nanoalgosomes that were used in the colocalization studies? I see in the materials & methods that 2 ug were added to cells in 12-well plates which can usually hold 1-2 mL, so I assume its the same concentration, but the actual concentration is not currently clear. Sorry if I missed it somewhere.

  3. Both fluorescence and confocal images showed that intracellular LAMP-1- and calnexin-positive compartments (green) did not co-localize with internalized PKH26-labeled vesicles, suggesting that lysosomes and ER were not involved in their intracellular trafficking.

    In panel A the algosome signal looks pretty ubiquitously dispersed. While the colocalization w/ CD63 is clear, I think the figure could benefit from showing the individual channels like in panel b. Its hard to tell if the algosome signal is excluded at sites of Lamp1 & Calnexin or if its just ubiquitous signal that isn't enriched at these sites.