Abstract
BACKGROUND: Cervical cancer is one of the most common cancers among women globally, and its treatments remain limited, urgently needing new strategies. In recent years, the use of enzyme-like Fe(3)O(4) nanoparticles (NPs) has exhibited promising antitumor potential due to their unique physicochemical properties and biocompatibility. However, the therapeutic effect of Fe(3)O(4) NPs is often limited by their surface hydrophobicity. Therefore, this study aimed to construct Fe(3)O(4)-CC3 co-assemblies to overcome surface hydrophobicity and enhance antitumor efficacy. METHODS: Our study designed Fe(3)O(4)-CC3 co-assemblies through a unique oil-in-water (O/W) emulsion restriction strategy. Using HeLa cells as the experimental model, the effect of Fe(3)O(4)-CC3 on cell proliferation was evaluated by Cell Counting Kit-8 (CCK-8) assay. Morphological changes were observed under an optical microscope. The impact of Fe(3)O(4)-CC3 on cell migration was assessed using the wound-healing assay, and the apoptosis rate was analyzed by flow cytometry. The protein levels of apoptosis protein (Caspase-3), autophagy protein (Beclin1, p62, and LC3-B), and PI3K/AKT/mTOR pathway were determined by Western blot. The expression level of LC3-B in cells was observed by confocal fluorescence microscopy. Anti-tumour activity of Fe(3)O(4)-CC3 co-assemblies was accessed by subcutaneous xeno-transplanted tumour model of human cervical cancer in nude mice. RESULTS: Compared to traditional NPs, these co-assemblies are inherently hydrophobic, but they transition to a hydrophilic characteristic through the incorporation of the cationic surfactant (DTAB) via hydrophobic interactions. Our results demonstrated that Fe(3)O(4)-CC3 co-assemblies were superior to Fe(3)O(4) NPs in inhibiting cell proliferation and migration. Flow cytometry and Western blot analyses indicated that Fe(3)O(4)-CC3 co-assemblies induced apoptosis by activating apoptosis-related proteins and inhibiting the PI3K/AKT/mTOR signaling pathway, exhibiting multiple anti-tumor mechanisms. CONCLUSIONS: Fe(3)O(4)-CC3 co-assemblies induced apoptosis and promoted autophagy, accompanied by the inactivation of PI3K/AKT/mTOR pathway in cervical cancer and further inhibited tumour growth, which may lead to new therapeutic choices for patients and promote the development of nanomedicine in cancer therapy.