Fe-doped polydopamine pickering emulsion as a nanoplatform for synergistic photothermal-ferroptosis immunotherapy in breast cancer

Abstract

Triple-negative breast cancer remains a formidable clinical challenge owing to its immunosuppressive microenvironment and inherently low immunogenicity. To address this, we developed a multifunctional Pickering emulsion (Fe-PDA-PE-R837) stabilized by iron-doped polydopamine (Fe-PDA) nanoparticles, which function dually as photothermal agents and localized iron donors, while the soybean oil core encapsulates the immunoadjuvant R837. The Fe-PDA nanoparticles exhibited uniform spherical morphology, excellent colloidal stability, and a broad absorption band extending to the NIR region. Upon 808 nm laser irradiation, the Fe-PDA shell generates local hyperthermia with a photothermal conversion efficiency of 38.5%, disrupts intracellular iron homeostasis to provoke ferroptotic cell death, as evidenced by GSH depletion and MDA accumulation, while the stimuli-responsive release of R837 coupled with immunogenic cell death (ICD) elicits potent local and systemic pro-inflammatory responses. In vitro assays demonstrated that the combination treatment achieved ∼80% cell killing, markedly inhibited cell migration, and significantly upregulated TNF-α and IL-12 secretion. In vivo evaluation using the 4T1 murine breast cancer model confirmed that this nanoplatform significantly suppressed primary tumor growth and pulmonary metastasis, with no appreciable systemic toxicity. Collectively, this interfacial engineering strategy underscores the promising translational potential of Pickering emulsion-based nanoplatforms for aggressive solid tumor therapy.