An E3 Aptamer-Modified T Cell-Derived Exosomal Nanoplatform for Codelivery of Astragaloside IV and PESV: Enhancing Prostate Cancer Therapy Through Immune Modulation with Implications for Clinical Translation.

内容摘要

Prostate cancer (PCa) remains a leading cause of cancer-related mortality in men, with current treatments often limited by drug resistance and systemic toxicity. Although traditional Chinese medicine components such as Astragaloside IV and polypeptide extract from scorpion venom (PESV) have demonstrated promising antitumor activity, their clinical translation is hampered by poor bioavailability and lack of tumor specificity. To address these limitations, we engineered an E3 aptamer-modified T cell-derived exosomal nanoplatform (EAPE) for the targeted co-delivery of Astragaloside IV and PESV in prostate cancer therapy. EAPE was constructed and characterized, and its targeting capability, biosafety, and therapeutic performance were evaluated in vitro and in vivo. In vitro, the antitumor efficacy was assessed by proliferation, migration and apoptosis assays, while the immunomodulatory effects were investigated using a co-culture system of LNCaP cells and T lymphocytes. In vivo, the antitumor efficacy and immune activation were examined in prostate cancer xenograft mouse model, with tumor growth inhibition, apoptosis and immune responses measured. EAPE demonstrated efficient tumor-targeting capability and favorable biosafety profiles both in vitro and in vivo. EAPE demonstrated superior therapeutic efficacy against PCa by inhibiting proliferation and migration of prostate cancer cells and inducing apoptosis, while suppressing immunosuppression and activating antitumor immune response. This study presents a biologically derived, targeted nanodelivery system that improves the delivery efficiency and therapeutic efficacy of Astragaloside IV and PESV. These findings support the potential of exosome-based nanoplatforms as promising strategies for enhancing the translational application of traditional Chinese medicine-derived therapeutics in prostate cancer.