Cathepsin B-sensitive drug delivery from redox responsive BSA nanoparticles

María Vallet Regí – Professor Emeritus, Department of Chemistry in Pharmaceutical Sciences, Universidad Complutense de Madrid; Miguel Gisbert-Garzarán – Assistant Professor, Department of Chemistry in Pharmaceutical Sciences, Universidad Complutense de Madrid

Introduction: Stimuli-responsive prodrugs hold the potential to minimize undesired drug release in healthy tissues. In this sense, the use of enzymes that are overexpressed in certain diseases constitutes a reliable stimulus. Cysteine protease cathepsin B (CPC B) is upregulated in certain types of cancer [1]. However, both the presence of the proteases in the extracellular matrix [2] and the capability of other CPCs to cleave VC-linkers [3] are a problem for the systemic delivery of these prodrugs. In this work, we propose a redox-sensitive nanoformulation that protects the prodrug until it is internalized in the cell, where the environment disassembles the nanoparticle, exposing the linker for enzyme cleavage.