iRGD-modified 3D exosomes delivering miR-99b-5p induce ferroptosis to inhibit colorectal cancer progression.

Colorectal cancer (CRC) remains a significant global health challenge, with current treatments often limited by systemic toxicity and drug resistance. Mesenchymal stem cell (MSC)-derived exosomes offer a promising nanocarrier platform for targeted drug delivery, capable of transporting therapeutic molecules with low immunogenicity. However, enhancing their therapeutic efficacy through functional modifications and improved bioactive molecule loading is crucial to overcome current limitations and improve patient outcomes in advanced CRC.

Researchers cultured MSCs under two-dimensional (2D) and three-dimensional (3D) conditions, isolating exosomes from the supernatants. Exosome characteristics and yields were assessed using nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), western blot analysis, and bicinchoninic acid (BCA) assay. Subsequently, 3D exosomes were loaded with miR-99b-5p and surface-modified with iRGD peptide to create iRGD-Exo-miR-99b-5p. The therapeutic effects on colorectal cancer (CRC) progression were evaluated through in vitro assays and an in vivo xenograft tumor model.