https://doi.org/10.1140/epje/s10189-023-00331-5
Regular Article - Living Systems
Smart design of universally decorated nanoparticles for drug delivery applications driven by active transport
1
The Department of Chemical Engineering, Ben-Gurion University of the Negev, 84105, Beer Sheva, Israel
2
The Stella and Avram Goren-Goldstein Department of Biotechnology Engineering Ben-Gurion University of the Negev, 84105, Beer Sheva, Israel
3
The Ilse Katz Institute for Meso and Nanoscale Science and Technology, Ben-Gurion University of the Negev, 84105, Beer Sheva, Israel
4
Department of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
5
Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, 3200008, Haifa, Israel
Received:
29
April
2023
Accepted:
25
July
2023
Published online:
31
August
2023
Targeting the cell nucleus remains a challenge for drug delivery. Here, we present a universal platform for the smart design of nanoparticle (NP) decoration that is based on: (i) a spacer polymer, commonly biotin-polyethylene-glycol-thiol, whose grafting density and molecular weight can be tuned for optimized performance, and (ii) protein binding peptides, such as cell penetrating peptides (CPPs), cancer-targeting peptides, or nuclear localization signal (NLS) peptides, that are linked to the PEG free-end by universal chemistry. We manifested our platform with two different bromo-acetamide (Br-Ac) modified NLSs. We used cell extract-based and live cell assays to demonstrate the recruitment of dynein motor proteins, which drive the NP active transport toward the nucleus, and the enhancement of cellular and nuclear entry, manifesting the properties of NLS as a CPP. Our control of the NP decoration scheme, and the modularity of our platform, carry great advantages for nano-carrier design for drug delivery applications.
© The Author(s), under exclusive licence to EDP Sciences, SIF and Springer-Verlag GmbH Germany, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
