2026-10-11T13:11:56Z https://www.scidb.cn/oai

10.57760/sciencedb.44767 2026-07-30T11:09:39Z

2026-07-30 Bioengineered ferritin-based lysosome-targeting chimera platform for tumor-targeted therapy doi:10.57760/sciencedb.44767 en Lysosome-targeting chimeras (LYTACs) hold therapeutic potential by degrading pathogenesis-associated proteins. However, current LYTAC systems often require considerable effort for case-by-case construction and are devoid of a convenient and efficient modular platform. Here, we develop a modular LYTAC platform based on human heavy chain ferritin (HFn), leveraging its peptide-display function and TfR1-mediated lysosomal endocytosis. This system comprises a bioengineered HFn scaffold with enhanced TfR1 affinity and target-specific affibodies conjugated to the HFn via SpyTag-SpyCatcher system. Using this approach, HFn-LYTACs efficiently degrade epidermal growth factor receptor, epidermal growth factor receptor-2 and programmed death-ligand 1. Mechanistic studies indicate that the HFn-LYTAC platform mediates the degradation of membrane proteins via two distinct mechanisms: a TfR1-dependent endocytic pathway as well as the nanoparticle size and multivalent ligand effect of HFn-LYTAC. In vivo, HFn-LYTACs inhibit tumor growth with favorable safety. Therefore, the modular HFn-LYTAC platform represents a versatile, efficient, and promising strategy for tumortargeted therapy. Bioengineered ferritin; lysosome-targeting chimera platform ; tumor-targeted therapy Fan Kelong PUBLIC https://creativecommons.org/publicdomain/zero/1.0/ dataset Science Data Bank