Abstract

In 2020, nearly 20 million peoples got cancer and nearly 10 million peoples died of cancer, indicating the cancer remains a great threat to human health and life. New therapies are still in urgent demand. We here develop a novel cancer therapy named Ferroptosis ASsassinates Tumor (FAST) by combining iron oxide nanoparticles with cancer-selective knockdown of seven key ferroptosis-resistant genes (FPN, LCN2, FTH1, FSP1, GPX4, SLC7A11, NRF2). We found that FAST had notable anti-tumor activity in a variety of cancer cells but little effect on normal cells. Especially, FAST eradicated three different types of tumors (leukemia, colon cancer, and lung metastatic melanoma) from over 50% of cancer mice, making the mice survive up to 250 days without tumor relapse. FAST also significantly inhibited and prevented the growth of spontaneous breast cancer and improved survival in mice. FAST showed high pan anti-tumor efficacy, high cancer specificity, and in vivo safety. FAST defines a new form of advanced nanomaterials, advanced combinatorial nanomaterials, by combining two kinds of nanomaterials, a chemical nanomaterial (iron oxide nanoparticles) and a biochemical nanomaterial (adeno-associated virus), which successfully turns a general iron nanomaterial into an unprecedented assassin to cancer.