Chlorella-derived extracellular vesicle-based nanogels suppress cGAS-STING for treatment of radiation-induced lung injury

Radiation-induced lung injury (RILI) represents a critical complication associated with radiation exposure, requiring targeted treatment strategies in clinical practice. Here, we pioneered the extraction of extracellular vesicles (EVs) from Chlorella and innovatively developed a multifunctional nanogel platform (RU.521-EVs NPs) by combining them with the cGAS inhibitor RU.521. The Chlorella-derived EVs possess a naturally high abundance of antioxidant enzymes (e.g., SOD2, CAT) and anti-inflammatory lipids (e.g., linolenic acid). RU.521-EVs NPs could synergistically inhibit excessive activation of the cGAS-STING pathway, and significantly reduce the secretion of pro-inflammatory factors. In the RILI mouse model, the nanogel demonstrated significant anti-inflammatory and anti-fibrosis activity, with no observed systemic toxicity. Their biological safety, cost-effectiveness, and multifaceted anti-radiation mechanisms of nanogels make them particularly beneficial in contexts such as medical radiation exposure, providing a strategy for the clinical translation of RILI that emphasizes both safety and long-term efficacy. Radiation-induced lung injury (RILI), a serious complication of radiation exposure, is associated with cGAS-STING pathway overactivation. Here, the authors developed a nanogel based on microalgal extracellular vesicles and a cGAS inhibitor to prevent and treat RILI and its progression to fibrosis.