Efficient Delivery of Biological Cargos into Primary Cells by Electrodeposited Nanoneedles via Cell-Cycle-Dependent Endocytosis

Zongjie Wang, Hansen Wang, Sichun Lin, Mahmoud Aziz Mahmoud Labib, Sharif Ahmed, Jagotamoy Das, Stephane Angers, Edward H. Sargent, Shana O. Kelley*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Nanoneedles are a useful tool for delivering exogenous biomolecules to cells. Although therapeutic applications have been explored, the mechanism regarding how cells interact with nanoneedles remains poorly studied. Here, we present a new approach for the generation of nanoneedles, validated their usefulness in cargo delivery, and studied the underlying genetic modulators during delivery. We fabricated arrays of nanoneedles based on electrodeposition and quantified its efficacy of delivery using fluorescently labeled proteins and siRNAs. Notably, we revealed that our nanoneedles caused the disruption of cell membranes, enhanced the expression of cell-cell junction proteins, and downregulated the expression of transcriptional factors of NFκB pathways. This perturbation trapped most of the cells in G2 phase, in which the cells have the highest endocytosis activities. Taken together, this system provides a new model for the study of interactions between cells and high-aspect-ratio materials.

Original languageEnglish (US)
Pages (from-to)5877-5885
Number of pages9
JournalNano letters
Volume23
Issue number13
DOIs
StatePublished - Jul 12 2023

Funding

This research was supported in part by the Canadian Institutes of Health Research (Grant FDN-148415) and the Natural Sciences and Engineering Research Council of Canada (Grant RGPIN-2016-06090). This research is part of the University of Toronto’s Medicine by Design initiative, which receives funding from the Canada First Research Excellence Fund. Z.W. was supported by an Alexander Graham Bell Canada Graduate Scholarship and a Centre for Pharmaceutical Oncology Graduate Student Scholarship.

Keywords

  • Electrodeposition
  • cell cycle
  • intracellular delivery
  • mechanobiology
  • nanostructure

ASJC Scopus subject areas

  • Condensed Matter Physics
  • Mechanical Engineering
  • Bioengineering
  • General Chemistry
  • General Materials Science

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