Intracellular self-aggregation of biomimetic Fe ₃ O ₄ nanoparticles for enhanced ferroptosis-inducing therapy of breast cancer

Nanomedicines based on ferroptosis may be effective strategies for cancer therapy due to their unique inducing mechanism. However, the challenges, including non-target distribution, poor accumulation and retention of nanomedicine, have a profound impact on the effectiveness of drug delivery. Here, we developed cancer cell membrane (CCM)-coated Fe₃O₄ nanoparticles (NPs) modified with supramolecular precursors and loaded with sulfasalazine (SAS) for breast cancer therapy. Benefiting from the coating of the CCM, these NPs can be specifically recognized and internalized by tumor cells rapidly after being administered and form aggregates via the host-guest interaction between adamantane (ADA) and cyclodextrins (CD), which in turn effectively reduces the exocytosis of tumor cells and prolongs the retention time. In vitro and in vivo studies showed that Fe₃O₄ NPs possessed effective cellular uptake and precise specific accumulation in tumor cells and tissues through CCM-targeted supramolecular in situ aggregation, demonstrating enhanced ferroptosis-inducing therapy of breast cancer. Overall, this work provided a supramolecular biomimetic platform to achieve targeted delivery of Fe₃O₄ NPs with high efficiency and precise self-assembly for improved cancer therapy.