Iron-siRNA Nanohybrids for Enhanced Chemodynamic Therapy via Ferritin Heavy Chain Downregulation

Angew Chem Int Ed Engl. 2023 Mar 23:e202302255. doi: 10.1002/anie.202302255. Online ahead of print.ABSTRACTFerrous iron (Fe2+) has more potent hydroxyl radical (•OH)-generating ability than other Fenton-type metal ions, making Fe-based nanomaterials attractive for chemodynamic therapy (CDT). However, because Fe2+ can be converted by ferritin heavy chain (FHC) to nontoxic ferric form and then sequestered in ferritin, therapeutic outcomes of Fe-mediated CDT agents are still far from satisfactory. Here we report the synthesis of siRNA-embedded Fe0 nanoparticles (Fe0-siRNA NPs) for self-reinforcing CDT via FHC downregulation. Upon internalization by cancer cells, pH-responsive Fe0-siRNA NPs are degraded to release Fe2+ and FHC siRNA in acidic endo/lysosomes with the aid of oxygen (O2). The accompanied O2 depletion causes an intracellular pH decrease, which further promotes the degradation of Fe0-siRNA NPs. In addition to initiating chemodynamic process, Fe2+-catalyzed •OH generation facilitates endo/lysosomal escape of siRNA by disrupting the membranes, enabling FHC downregulation-enhanced CDT.PMID:36959091 | DOI:10.1002/anie.202302255

Source: Angewandte Chemie - March 23, 2023 Category: Chemistry Authors: Jun Wang Hongye Ding Yang Zhu Yina Liu Meili Yu Huilan Cai Rujiang Ao Hongwei Huang Peng Gong Yaxin Liao Zhaolin Chen Lisen Lin Xiaoyuan Chen Huanghao Yang Source Type: research