Super-resolution mapping of nuclear stress signaling by probiotic-derived extracellular vesicles in UV-induced skin photodamage

Ultraviolet (UV)-induced photodamage drives oxidative stress, DNA damage, and chronic inflammation, leading to progressive cellular ultrastructure and skin function degeneration. Despite the potential of probiotics as anti-photodamage agents, their nanoscale action mechanism remains unexplored. Here, we utilize super-resolution fluorescence microscopy to investigate the cellular and molecular basis of Lactobacillus plantarum -derived extracellular vesicles ( L. plantarum EVs) in mitigating photodamage. We showed that UV irradiation triggered extensive organellar remodeling along with elevated reactive oxygen species production, DNA damage signaling, and inflammatory activation. Remarkably, pre- and posttreatment with L. plantarum EVs preserved organelle integrity and restored native nanoscale architecture. Additionally, EV treatment delayed UV-induced PARP-1 activation and nuclear condensate clustering, while suppressing NF-κB translocation and downstream inflammatory cytokine expression. These findings establish probiotic-derived EVs as modulators of stress-responsive signaling and structural homeostasis during UV-induced photodamage. By providing a super-resolution mechanistic framework for understanding probiotic EV-mediated modulation of cellular photodamage responses, this study provides a basis for future investigation of EV-based strategies for skin protection.