Tutorial: using nanoneedles for intracellular delivery

Ciro Chiappini, Yaping Chen, Stella Aslanoglou, Anna Mariano, Valentina Mollo, Huanwen Mu, Enrica De Rosa, Gen He, Ennio Tasciotti, Xi Xie, Francesca Santoro, Wenting Zhao, Nicolas H. Voelcker, Roey Elnathan

Research output: Contribution to journalReview articlepeer-review

24 Scopus citations


Intracellular delivery of advanced therapeutics, including biologicals and supramolecular agents, is complex because of the natural biological barriers that have evolved to protect the cell. Efficient delivery of therapeutic nucleic acids, proteins, peptides and nanoparticles is crucial for clinical adoption of emerging technologies that can benefit disease treatment through gene and cell therapy. Nanoneedles are arrays of vertical high-aspect-ratio nanostructures that can precisely manipulate complex processes at the cell interface, enabling effective intracellular delivery. This emerging technology has already enabled the development of efficient and non-destructive routes for direct access to intracellular environments and delivery of cell-impermeant payloads. However, successful implementation of this technology requires knowledge of several scientific fields, making it complex to access and adopt by researchers who are not directly involved in developing nanoneedle platforms. This presents an obstacle to the widespread adoption of nanoneedle technologies for drug delivery. This tutorial aims to equip researchers with the knowledge required to develop a nanoinjection workflow. It discusses the selection of nanoneedle devices, approaches for cargo loading and strategies for interfacing to biological systems and summarises an array of bioassays that can be used to evaluate the efficacy of intracellular delivery.

Original languageEnglish (US)
Pages (from-to)4539-4563
Number of pages25
JournalNature Protocols
Issue number10
StatePublished - Oct 2021

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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