Regular Article - Living Systems
Smart design of universally decorated nanoparticles for drug delivery applications driven by active transport
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
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.
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