Year: 2025
Type: article
Abstract: Targeted protein degradation strategies have emerged as a promising approach for addressing undruggable membrane proteins by redirecting them to the cell's degradation machinery. Traditionally, this has been achieved through antibody-based constructs that hijack the endocytic pathways. More recently, nanoparticles have been proposed as a modular platform for surface protein scavenging, offering tunable properties and multivalent targeting. However, the extent to which nanoparticle physicochemical features influence degradation efficacy remains to be elucidated. In this study, we set up a high-content imaging workflow to screen a diverse library of antibody-functionalized nanoparticles varying in material composition, size, and targeting modality. Our results reveal that specific combinations of nanoparticle properties induce efficient receptor scavenging, allowing us to understand structure-activity relations better. These findings highlight the complex interplay between nanoparticle design and biological response and demonstrate the value of our high-throughput platform for guiding the rational design of nanoparticle-based protein degraders.
Source: Nanoscale Advances
DOI: 10.1039/d5na00811e
Authors: Joppe Oldenburg, Marrit M. E. Tholen, Janne G. D. Donkers, Ana Ortiz-Perez, Valentina Girola, Lorenzo Albertazzi
Institution: Eindhoven University of Technology
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,962
Award: G1683703664
OpenAlex ID: W4416270675