Red blood cell membrane-camouflaged nanocarriers for the delivery of piperlongumine to treat triple-negative breast cancer

The application of the conventional drugs for triple-negative breast cancer (TNBC) treatment in chemotherapy is limited due to their intrinsic drawbacks such as short drug half-life, lack of tumor selectivity and systemic toxicity. Herein, an effective nanoparticle drug delivery system (NDDS) of red blood cell (RBC) membrane-camouflaged piperlongumine (PL)-loaded iron oxide (Fe₃O₄) magnetic nanoparticles (Fe₃O₄-PL@RBC) was rationally designed as an effective drug delivery platform for<i>in vivo</i>TNBC treatment. The Fe₃O₄-PL@RBC showed considerable cytotoxicity against MDA-MB-231 cells, inducing intracellular accumulation of reactive oxygen species, mitochondrial dysfunction and apoptosis. Furthermore, transcriptomic analyses and western blotting analysis demonstrated that the Fe₃O₄-PL@RBC induced apoptosis through the inhibition of PI3K/AKT/mTOR pathway and downregulation of Bcl-2 protein. In MDA-MB-231 tumor models, the RBC membrane coating in Fe₃O₄-PL@RBC effectively prolonged the circulation time and sufficient enrichment at the tumor sites. And the Fe₃O₄-PL@RBC significantly inhibited tumor growth with good biosafety. This study provides guidance for the rational design of effective Fe₃O₄-based NDDS for TNBC treatment.