Search

Abstract Organoids are “mini-organs” that self-organize and differentiate from stem cells under in vitro 3D culture conditions, mimicking the spatial structure and function of tissues in vivo. Extracellular vesicles (EVs) are nanoscale phospholipid bilayer vesicles secreted by living cells, rich in bioactive molecules, with excellent biocompatibility and low immunogenicity. Compared to EVs, organoid-derived EVs (OEVs) exhibit higher yield and enhanced biological functions. Organoids possess stem cell characteristics, and OEVs are capable of delivering active substances, making both highly promising for medical applications. In this review, we provide an overview of the fundamental biological principles of organoids and OEVs, and discuss their current applications in disease treatment. We then focus on the differences between OEVs and traditional EVs. Subsequently, we present methods for the engineering modification of OEVs. Finally, we critically summarize the advantages and challenges of organoids and OEVs. In conclusion, we believe that a deeper understanding of organoids and OEVs will provide innovative solutions to complex diseases. Graphical Abstract

Abstract Background Osteoporosis is characterized by an imbalance in bone homeostasis, resulting in the excessive dissolution of bone minerals due to the acidified microenvironment mediated by overactive osteoclasts. Oroxylin A (ORO), a natural flavonoid, has shown potential in reversing osteoporosis by inhibiting osteoclast-mediated bone resorption. The limited water solubility and lack of targeting specificity hinder the effective accumulation of Oroxylin A within the pathological environment of osteoporosis. Results Osteoclasts’ microenvironment-responsive nanoparticles are prepared by incorporating Oroxylin A with amorphous calcium carbonate (ACC) and coated with glutamic acid hexapeptide-modified phospholipids, aiming at reinforcing the drug delivery efficiency as well as therapeutic effect. The obtained smart nanoparticles, coined as OAPLG, could instantly neutralize acid and release Oroxylin A in the extracellular microenvironment of osteoclasts. The combination of Oroxylin A and ACC synergistically inhibits osteoclast formation and activity, leading to a significant reversal of systemic bone loss in the ovariectomized mice model. Conclusion The work highlights an intelligent nanoplatform based on ACC for spatiotemporally controlled release of lipophilic drugs, and illustrates prominent therapeutic promise against osteoporosis.