Ferritin And HSA Based Nano-composite For Targeted RSL3 Delivery And Ferroptosis Induced Cancer Therapy

Cancer remains one of the most horrible threat to human health,and current cancer treatments include radiation therapy,chemotherapy and surgical treatment,but those traditional therapies rarely worked in breast cancer,especially the triple negative breast cancer(TNBC).TNBC is aggressive due to its high proliferation and frequent metastasis.Thus,there is an urgent need to find new therapies to cure TNBC.RSL3 is a small molecular which can induce ferroptosis,and human serum albumin(HSA)can load RSL3 via hydrophobic interaction.Here we designed a new method to combine ferritin and drug-loaded HSA to form a nanoparticle composite,which is termed as ferritin@HSARSL3.Ferritin can be precisely targeted to the transferritin receptor 1 of MDA-MB-231,and will release Fe after degraded in lysosome.The released RSL3 is capable of inducing ferroptosis via inhibiting the activity of GPX4,and the surplus Fe will enhance the ferroptosis.Ultimately,the synergistic effect of RSL3 and Fe leads the accumulation of lipid ROS and cell death.It developed a facile way for RSL3-loaded albumin and ferritin nanoparticle preparation and broke a new ground for composite nanoparticles which are based on different proteins.