Thylakoid-Based Photosynthetic Biomedicine: Discovery,Progression, and Challenges

Abstract Thylakoids are photosynthetic membrane systems located within the chloroplast of plants and algae, and thylakoid-derived materials have recently been established as a distinctive class of bionanomaterials for disease therapy. Unlike conventional phytochemical extraction or passive drug delivery, thylakoid-based systems preserve the native photosynthetic electron transport chain. This enables light- or ultrasound-driven production of O2, ATP, and NADPH. These bioenergetic outputs directly counter the pathological hallmarks of hypoxia, oxidative stress, energy deficiency, and inflammatory dysregulation. Such features are central to cancer, musculoskeletal degeneration, acute metabolic organ injury, thromboischemic disorders, and surface-accessible diseases. This review systematically examines the progression of thylakoid-based biomedicine from discovery to therapeutic application. We first discuss fabrication strategies for thylakoid-derived nanosystems, including nanothylakoid preparation, nanoparticle coating, cell-membrane hybridization, and three-dimensional matrix integration. We then classify disease applications by therapeutic mechanism. In oncology, thylakoid systems supply oxygen to enhance the efficiency of photodynamic therapy. In degenerative and ischemic diseases, they replenish ATP and NADPH to restore metabolic homeostasis. Despite these advances, clinical translation is still constrained by unaddressed challenges, including activation depth, membrane stability, immunogenicity, manufacturing scalability, and long-term biosafety. We conclude by outlining future directions. These include long-wavelength photosynthetic systems, ultrasound-responsive activation, synthetic biology-enabled artificial chloroplasts, and standardized manufacturing frameworks. By combining plant physiology with nanomedicine and metabolic therapy, thylakoid-inspired systems serve as a versatile, translatable platform for next-generation precision therapeutics.