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

INTRODUCTION

Triple-negative breast cancer remains a formidable clinical challenge owing to its immunosuppressive microenvironment and inherently low immunogenicity.

METHODS

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.

RESULTS

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.

DISCUSSION: Collectively, this interfacial engineering strategy underscores the promising translational potential of Pickering emulsion-based nanoplatforms for aggressive solid tumor therapy.