Recently, Prof. Sun Xiaolian 's team from the School of Pharmacy, CPU published their latest research in the top international journal, the American Chemical Society (JACS, impact factor 15.419), with the title “Renal Clearable Ultrasmall Single-Crystal Fe Nanoparticles for Highly Selective and Effective Ferroptosis Therapy and Immunotherapy”. Prof. Sun Xiaolian is the sole corresponding author, PhD student Liang Huan and M.S. student Wu Xiyao are the co-first authors and China Pharmaceutical University is the sole corresponding institution.
Iron-based nanoparticles have attracted much attention because of their ability to induce ferroptosis. However, current iron-based nanoparticles need to be used in cooperation with other treatments or be applied in a high dose for effective therapy because of their low reactive oxygen species production efficacy in tumor acidic microenvironments. Sun’s team proposed a new method to synthesize 2 nm ultrasmall single-crystal Fe nanoparticles (bcc-USINPs) that stayed stable in a normal physiological environment but were highly active in a tumor microenvironment because of the selective acidic etching ofan Fe3O4 shell and the exposure of the 0.7 nm Fe(0) core. (KM = 0.031 mM, Vmax = 5.92 ×10-7 M s-1)
The 2nm about bcc-USINPs could efficiently induce tumor cell ferroptosis and immunogenetic cell death at a very low concentration（IC50=15.72 μg/mL）. Intravenous injection of iRGD-bcc-USINPs at three doses of 1 mg/kg could effectively suppress the tumor growth, promote the maturation of dendritic cells, and trigger the adaptive T cell response. Combined with programmed death-ligand 1 (PD-L1) immune checkpoint blockade immunotherapy, the iRGD-bcc-USINP-mediated ferroptosis therapy greatly potentiated the immune response and developed strong immune memory. In addition, these USINPs were quickly renal excreted with no side effects in normal tissues. These iRGD-bcc-USINPs provide a simple, safe, effective, and selectively tumor-responsive Fe(0) delivery system for ferroptosis-based immunotherapy.
This research was supported by the National Key R&D Program of China (2016YFA0203600), the National Natural Science Foundation of China (81971738, 81571743), the State Key Laboratory of Natural Medicines Project of China Pharmaceutical University (SKLNMZZ202010), and the Key Laboratory of Drug Quality Control and Pharmacovigilance of China Pharmaceutical University (DQCP20/21MS02).
Paper Link：https://pubs.acs.org/doi/10.1021/jacs.1c07471
