ROS-Responsive Nano-Encapsulated Selenium Targeting Cervical Cancer Cell via PI3K/AKT Signaling Pathway.

PURPOSE: Current cervical cancer treatments have yet to realize significant advances in patient quality of life. To overcome the challenges of off-target toxicity and inefficient delivery, we developed targeted ROS-responsive selenium nanoparticles, based on selenium's anticancer properties. METHODS: FA-ReRSeNPs were synthesized and subjected to systematic characterization of their physicochemical and biological properties. The anti-tumor activity of FA-ReRSeNPs, along with the mechanistic basis, was validated using integrated in vitro assays and in vivo animal models. RESULTS: Using human cervical cancer cells (Hela and SiHa) and a SiHa subcutaneous xenograft nude mouse model, we verified that FA-ReRSeNPs significantly reduced the selenium dose required for anticancer activity, while alleviating off-target damage to normal tissues. Mechanistic studies confirmed that FA-ReRSeNPs exert anticancer effects via inhibition of PI3K/AKT signaling pathway; this inhibition subsequently induces tumor cell apoptosis and restrains proliferation. Cross-validated results from in vitro assays and in vivo burden analyses demonstrate that FA-ReRSeNPs possess superior tumor-inhibitory potential with high targeting specificity. CONCLUSION: This work confirms FA-ReRSeNPs as a precision-driven nanotherapeutic for cervical cancer management. The fusion of active targeting and ROS-responsive release mechanisms addresses the classic efficacy-toxicity dilemma of conventional anticancer agents, highlighting the translational value of intelligent nanoengineering in advancing cancer therapies.