Kaempferol–Iron Assembled Nanoparticles for Synergistic Photothermal and Chemodynamic Therapy of Breast Cancer

Photothermal and chemodynamic therapies (PTT and CDT) have gained traction as viable adjunct anti-cancer treatments. However, they remain restricted by the low efficiency of photothermal conversion and the inefficiency of the Fenton reaction. Kaempferol (Kae), a naturally occurring bioactive flavonoid, can induce apoptotic signaling pathways by reducing the expression or activity of many proteins involved in the initiation and execution phases of apoptosis. In this study, we fabricated Kae–iron-assembled nanoparticles (Kae-Fe NPs) for synergistic PTT and CDT in breast cancer treatment. Under 808 nm laser irradiation, the Kae-Fe NPs not only facilitated the photon-to-heat energy conversion for PTT but also enhanced CDT by improving the efficiency of the Fenton reaction. Additionally, treatment with Kae-Fe NPs induced the release of immunostimulatory signals from breast cancer cells, leading to the migration of HMGB1 and CRT protein expression, and the release of ATP into the extracellular space, thereby triggering immunogenic cell death (ICD) and macrophage polarization toward the M1 type. The implications of these results are that Kae-Fe NPs have a dual effect: reprogramming macrophage phenotypes and inducing ICD. Furthermore, this study lays a firm foundation for utilizing Kae-Fe NPs in breast cancer management.