Functionalized Red Blood Cell Membrane Nanoplatform for Paclitaxel and Artesunate Induces Ferroptosis and Immunogenic Cell Death against Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) tends to exhibit extremely large rates of tumor recurrence and mortality owing to the absence on effective therapeutic targets. Paclitaxel is the chemotherapeutic drug of choice, but the clinical efficacy in TNBC is limited. In the present study, we developed a folic acid (FA)-modified red blood cell membrane biomimetic drug delivery system encapsulating both paclitaxel and artesunate (PA@LRM-FA) against TNBC, aimed at enhancing ferroptosis and promoting immunogenic cell death to improve paclitaxel efficacy. The morphology, particle size, zeta potential, particle stability, paclitaxel and artesunate loading capacity, and paclitaxel and artesunate encapsulation efficiency of the formulations were studied. Through a cellular assay, we discovered that PA@LRM-FA inhibited the 4T1 cell proliferation, induced ROS accumulation, and promoted ferroptosis and immunogenic cell death. In tumor-bearing mice, PA@LRM-FA effectively targeted tumor tissues for the delivery of paclitaxel and artesunate and significantly induced ferroptosis, promoting immunogenic cell death and active immune cells in 4T1 tumors, resulting in a marked inhibition of tumor growth. Taken together, this work demonstrated a feasible therapeutic approach to inhibit TNBC by enhancing tumor ferroptosis and immunogenic cell death through PA@LRM-FA delivery of paclitaxel and artesunate.