Mechanical Threshold-Guided Harvesting of Microalgal Therapeutics via Designer Nanovesicles

Microalgae encapsulate extensive concentrations of bioactive metabolites within structurally recalcitrant cell walls that impede conventional extraction methodologies. Here we demonstrate a biomimetic strategy that exploits cellular elasticity to generate microalgae-derived nanovesicles (MNVs) with preserved therapeutic functionality. Using representative microalgae species with distinct wall architectures, we establish through atomic force microscopy and micropipette aspiration that vesicle production efficiency inversely correlates with cellular elasticity. Critical mechanical thresholds of ∼100 kPa (localized membrane properties) and ∼390 kPa (global) govern successful vesiculation. The resulting MNVs retain species-specific carotenoid profiles and exhibit enhanced antioxidant capacity compared to parent cells. Zeaxanthin-enriched MNVs demonstrate superior cytoprotection in oxidative-stressed keratinocytes, effectively modulating MAPK signaling and reducing intracellular reactive oxygen species. In reconstructed human epidermis models, MNVs preserve tissue architecture and redox homeostasis under UV-induced oxidative damage. This mechanically guided approach provides a scalable platform for harnessing microalgal therapeutics in biocompatible delivery systems.