Oral Squamous Cell Carcinoma (OSCC) is a highly invasive malignant tumor with poor prognosis, and its treatment faces severe challenges due to the widespread presence of chemoresistance. Ferroptosis, a unique iron-dependent regulated cell death mode, has emerged as a highly promising target to bypass traditional apoptotic pathways and overcome therapeutic resistance in OSCC. Circular RNAs (circRNAs), a class of non-coding RNAs with covalent closed-loop structures and high stability, exhibit significant dysregulation in OSCC and deeply participate in tumor progression as key regulatory nodes. This review systematically elaborates on the core molecular mechanisms by which circRNAs regulate ferroptosis in OSCC and explores their potential as diagnostic biomarkers and therapeutic targets. Studies have shown that specific oncogenic circRNAs (such as circFNDC3B and circ_0000140) can upregulate the expression of SLC7A11, a key subunit of System Xc⁻, by acting as microRNA (miRNA) sponges, thereby inhibiting ferroptosis and ultimately promoting the malignant progression of OSCC and resistance to chemotherapeutic drugs such as cisplatin. Therefore, targeting this "circRNA-miRNA-SLC7A11" regulatory axis provides an innovative therapeutic strategy to reverse OSCC resistance. However, the clinical translation of circRNAs is limited by their in vivo delivery efficiency and targeting ability. To this end, nanomaterial-based delivery systems, such as lipid nanoparticles (LNPs) and polymeric nanoparticles, with advantages of enhanced stability, targeted delivery, and reduced immunogenicity, offer an ideal solution for the precise and efficient delivery of therapeutic circRNAs. Through engineering design, nanocarriers can even synergize with circRNA payloads to co-induce ferroptosis, thereby maximizing therapeutic effects. Despite the challenges in specificity, potential toxicity, and large-scale production in this field, nanomaterial-mediated circRNA ferroptosis-inducing therapy represents a transformative multimodal synergistic therapeutic paradigm with the potential to overcome the bottlenecks in OSCC treatment.

Wang Muhan. Nanomaterials-Loaded circRNAs Influence Oral Squamous Cell Carcinoma by Regulating Ferroptosis: Mechanisms, Therapeutic Potential, and Future Perspectives. Academic Journal of Medicine & Health Sciences (2025), Vol. 6, Issue 8: 118-130. https://doi.org/10.25236/AJMHS.2025.060816.

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