The fucoidan delivery system enhanced the anti-cervical cancer effect of caffeic acid

Cervical cancer remains one of the leading causes of mortality among women, and immunotherapy targeting the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway holds promise for its treatment. This study has developed nanoparticles based on fucoidan (Fu/CA NPs), successfully loading them with caffeic acid (CA) for application in cervical cancer therapy. In vitro experiments revealed that Fu/CA NPs significantly inhibited the proliferation of cervical cancer HeLa cells (by 65.73 ± 4.06 %) and induced apoptosis through the accumulation of reactive oxygen species and mitochondrial damage. Furthermore, treatment with Fu/CA NPs activated the cGAS-STING pathway, attributed to the cytoplasmic release of mitochondrial DNA (mtDNA) and the induction of DNA double-strand breaks (dsDNA) by Fu/CA NPs. In vivo results confirmed that Fu/CA NPs suppressed solid tumor growth (by 67.8 %), with even more pronounced antitumor effects observed when combined with cisplatin (96.5 %), a phenomenon also associated with the activation of the cGAS-STING pathway. Excitingly, the combination of Fu/CA NPs and cisplatin alleviated cisplatin-induced nephrotoxicity, as indicated by a decrease in blood urea nitrogen (BUN) by 53.27 % and serum creatinine (SCr) by 74.93 %. In summary, our research presents a potential therapeutic avenue for cervical cancer treatment, particularly highlighting the synergistic benefits of combining Fu/CA NPs with cisplatin.