Scheme 1
a Schematically illustrates the Fe-miR-122/DOX nanocomplex assembly through a FeII-ion-driven coordination process involving DOX and DNA molecules. b The therapeutic mechanism of the Fe-miR-122/DOX complex in HCC is elucidated: upon HepG2 cell uptake, the complex escapes the endosome, releasing miR-122 and DOX into the cytosol. MiR-122 exerts dual actions; it downregulates P-glycoprotein (P-gp) (I), reducing extracellular efflux of doxorubicin, while inhibiting Bcl-2 expression (II), thereby enhancing caspase-3 expression to promote apoptosis. Simultaneously, DOX translocates to the nucleus (III), effectively inhibiting cIAPs-mediated anti-apoptotic signaling, reducing PARP-1 expression, inducing DNA damage, ultimately yielding a synergistic antitumor effect