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Smart design of universally decorated nanoparticles for drug delivery applications driven by active transport

  • Regular Article - Living Systems
  • Published:
The European Physical Journal E Aims and scope Submit manuscript

Abstract

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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Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Abbreviations

B-PEG-SH:

 biotin-polyethylene-glycol-thiol

BSA:

Bovine serum albumin

Br-Ac:

Bromo-acetamide

CE:

Hela cells extract

CPP:

Cell penetrating peptides

CPT:

Cancer-targeting peptides

MPBP:

Motor protein binding peptide

MT:

Microtubule

Ne-Avidin:

 Neutravidin

NLS:

Nuclear localization signals

NP:

Nanoparticles

TAMRA:

Tetramethylrhodamine

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Acknowledgements

This research was initially supported (to A.B, R.G., and A.B.-G.) by the Focal Technological Area Program of the Israeli National Nanotechnology Initiative (INNI). The authors thank Dr. Einat Roth Nativ and Dr. Alexander Upcher for NP imaging by cryo-TEM.

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Authors and Affiliations

  1. The Department of Chemical Engineering, Ben-Gurion University of the Negev, 84105, Beer Sheva, Israel

    Gal Halbi, Dina Aranovich, Shachar Gat & Anne Bernheim-Groswasser

  2. The Stella and Avram Goren-Goldstein Department of Biotechnology Engineering Ben-Gurion University of the Negev, 84105, Beer Sheva, Israel

    Itay Fayer & Rony Granek

  3. The Ilse Katz Institute for Meso and Nanoscale Science and Technology, Ben-Gurion University of the Negev, 84105, Beer Sheva, Israel

    Mariela J. Pavan, Daniel Sevilla Sanchez, Rony Granek & Anne Bernheim-Groswasser

  4. Department of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel

    Dikla Nachmias

  5. Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, 3200008, Haifa, Israel

    Ashraf Brik

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  1. Gal Halbi
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  2. Itay Fayer
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Contributions

G.H. Performed experiments, analyzed the experimental results, prepared the Figures and Movies, and wrote the manuscript. I.F. Performed computer simulations and developed analytical tools for data quantification of NP active transport. D.A. Designed, performed, and analyzed the WB experiments. S.G. Rational design and development of the NP cargo. M.J.P. Performed and analyzed the Raman experiments. D.N. Performed the live cell experiments. D.S.S. Image analysis of the live cell experiments. A.B. Designed and synthesized the NLS peptides. R.G. Developed the theoretical model and computer simulations, and wrote the manuscript. A.B.G. Rational design and development of the NP cargo, developed the analytical tools for data quantification and NP active transport, and wrote the manuscript.

Corresponding author

Correspondence to Anne Bernheim-Groswasser.

Additional information

This article is dedicated to Fyl Pincus whose scientific achievements and contributions in condensed and soft matter, polymers, polyelectrolytes, colloids, electrostatic effects, and biological physics had a huge impact on our entire community, and on Rony and Myself, in particular. Festschrift in honor of Philip (Fyl) Pincus. Guest editors: Jean-Marc Di Meglio, David Andelman, and Cyrus R. Safinya.

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Halbi, G., Fayer, I., Aranovich, D. et al. Smart design of universally decorated nanoparticles for drug delivery applications driven by active transport. Eur. Phys. J. E 46, 74 (2023). https://doi.org/10.1140/epje/s10189-023-00331-5

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