Solanum nigrum-derived nanovesicles as novel nanotherapeutics suppressing prostate cancer progression via senescence-based antitumor activity

Background Current prostate cancer (PCa) therapies often encounter significant challenges due to adverse effects and eventual drug resistance, highlighting the need for novel therapeutic approaches. Here, we first isolated Solanum nigrum-derived nanovesicles (SDNVs) and explored their antitumor effects and underlying mechanisms against prostate cancer. Methods SDNVs were isolated via ultracentrifugation combined with sucrose gradient purification and characterized using nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), as well as protein and RNA analyses. Cellular uptake, antitumor activity, and safety of SDNVs were evaluated in prostate cancer PC-3 cells and normal prostate epithelial RWPE-1 cells. A subcutaneous PC-3 xenograft mouse model was established to determine in vivo efficacy and biodistribution. Transcriptomic sequencing, qPCR, Western blotting, and rescue experiments with the p53 inhibitor PFT-α were performed to clarify the molecular mechanisms. Results SDNVs were efficiently internalized by PC-3 cells, significantly inhibiting cell viability, proliferation, and migration while promoting apoptosis. Transcriptomic analysis and experimental validation demonstrated that SDNVs selectively triggered cellular senescence in PC-3 cells through activation of the p53/p21 signaling pathway. Importantly, SDNVs did not induce senescence or cytotoxicity in normal RWPE-1 cells, suggesting favorable tumor-selective properties. Oral administration of SDNVs markedly suppressed tumor growth in vivo, with no obvious toxicity in major organs. Conclusion SDNVs are biocompatible, plant-derived nanotherapeutics capable of selectively inhibiting prostate cancer growth through senescence induction. This study supports the further development of SDNVs as a safe and effective antitumor strategy targeting tumor-specific senescence pathways.