Size dependent PASylation critically regulates H-Ferritin nanocage stability and functionality

Beatrice Bignami – Fellow, Dipartimento di Scienze Biomediche e Cliniche, Università degli Studi di Milano; Francesca Gorgoglione – Fellow, Dipartimento di Scienze Biomediche e Cliniche, Università degli Studi di Milano; Valeria Giacobbo – Post-doctoral fellow, Dipartimento di Scienze Biomediche, Università di Milano; Marta Sevieri – Post-doctoral fellow, Dipartimento di Scienze Biomediche e Cliniche, Università degli Studi di Milano; Claudia Pigliacelli – Prof., Department of Chemistry, Materials and Chemical Engineering “Giulio Natta”, Politecnico di Milano; Francesca Baldelli Bombelli – Prof., Department of Chemistry, Materials and Chemical Engineering “Giulio Natta”, Politecnico di Milano; Renata Tisi – Prof., Dipartimento di Biotecnologie e Bioscienze, Università degli Studi di Milano-Bicocca; Fabio Corsi – Prof., Department of Biomedical and Clinical Sciences, University of Milan

Introduction:

H‑ferritin nanocages (HFn) are promising tumor‑targeted drug delivery systems, but their rapid clearance limits clinical translation [1,2]. PASylation extends circulation time while preserving receptor‑mediated uptake, yet only PAS domains ≥40 amino acids have been explored [3]. Here, we investigate how shortening the PAS sequence affects HFn assembly, structural stability, and functional performance [4].