Fig-derived exosome-like nanoparticles attenuating bone metastasis of breast cancer through establishing an anti-tumor microenvironment.

Plant-derived exosomes-like nanoparticles (ELNs) have been proven to be utilized as a promising therapy for varieties of diseases and conditions with ideal biocompatibility and biosecurity. Fig (Ficus carica) was reported to exert an anti-tumor effect, however, the active components and the underlying mechanism are still unclear. Herein, we isolated and characterized Fig-releasing ELNs (Fig-ELNs). Then, we found Fig-ELNs can prevent the growth of both human and murine breast cancer (BC) cells and induce M1 polarization of macrophages in bone metastasis murine model of BC. Mechanically, peu-miR-2916-p3 was identified as the important component in Fig-ELNs to inhibit the progression of bone metastasis of BC. Peu-miR-2916-p3 can promote the degradation of RN7SL1 and induce the apoptosis of BC cells. On the other hand, it also directly targeted Stab1 and promote the activation of non-canonical NF-κB pathway to facilitate M1 polarization. Our study demonstrated that Fig-ELNs can be a promising therapeutical target of bone metastasis of BC through directly inhibiting the growth of BC cells and remodeling tumor microenvironment, implying as safe and effective adjuvant therapy.