061 | Immunosafe(r)-by-design invertebrate-based nanoparticles: from engineered to biogenic structures for translational nanomedicine

Annalisa Pinsino¹, Giovanni Perconti¹, Alessia Giannetto², Andi Alijagic³ | ¹Institute of Translational Pharmacology IFT, National Research Council CNR, Palermo, Italy; ²Department of Chemical, Biological, Pharmaceutical and Environmental Sciences ChiBioFarAm, University of Messina, Italy; ³Man-Technology-Environment Research Center MTM, Orebro University, Sweden.

Nanotechnology research covers a wide range of studies focusing on designing and shaping new engineering materials, systems, and devices at the nanoscale, with unique size-dependent properties and applications. The value and potential of engineered nanoparticles (NPs) in human diagnostics and therapies rely on their safety and biocompatibility. These nanostructures undergo complex interactions with the surrounding biological environment, leading to remarkable changes in their “biological identity” and dictating particle behavior and fate, including uptake, pharmacokinetics, and toxicity. NPs quickly bind to macromolecules in the extracellular environment, forming a complex, dynamic external layer (mainly the protein corona) before contacting cells and tissues, becoming biogenic. The formation of a custom-made protein corona is the first signal of their interplay with a cell, and immune reactions are a major issue for their application in medicine. Similarly, natural biogenic NPs (e.g., extracellular vesicles) shuttle a complex molecular cargo that reflects the physiology of their cell of origin and influences cell-extracellular vesicle (EV) interaction and cellular behavior. The interest in tools that utilize natural bioactive molecules and offer innovative solutions to prevent and treat diseases is increasing, and the development of invertebrate-based NPs may provide an opportunity to obtain NPs with selective biological activities using an alternative, safe, economical, and eco-friendly approach (the green approach). Adopting alternative models (e.g., invertebrates) and methodology that promote the 3 R principles (reduce, refine, and replace) is gaining momentum. Based on our current studies, the sea urchin extracellular proteins form a corona on the particle surface, eliciting a selective immunological response in the sea urchin (Alijagic et al. 2019 doi: 10.3389/fimmu.2019.02261, Alijagic et al. 2021 doi: 10.1016/j.jhazmat.2020.123793, Pinsino & Di Bernardo 2022 doi: 10.1016/bs.apcsb.2022.01.002) as well as driving NPs, sea urchin immune cells, and the host microbiota interaction in vitro (Alijagic et al. 2025 doi: 10.1016/j.jhazmat.2024.136808). Research on EVs derived from different species, especially those living in challenging environmental conditions (e.g., sea urchins in the sea, black soldier flies in the waste), can lead to the development of high-value-added therapeutics, and this is the focus of our ongoing studies. We addressed the issue by isolating and characterizing EVs released into the blood of two invertebrate models, the sea urchin Paracentrotus lividus and the black soldier fly Hermetia illucens, under physiological and challenging conditions, and evaluating their impact on representative human pathological states (e.g., breast cancer cells) using Cell painting-based phenomics at high throughput. The results are very encouraging, and they set the stage for long-term future planning.
Studies were supported by the EU H2020 project PANDORA (GA 671881), the MUR-PNRR project SAMOTHRACE (GA ECS00000022), and the MUR-PNRR PRIN 2022. Project SURPRISE (GA P2022LASKT).