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Porous silicon nanoneedles modulate endocytosis to deliver biological payloads

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Title: Porous silicon nanoneedles modulate endocytosis to deliver biological payloads
Authors: Gopal, S
Chiappini, C
Penders, J
Leonardo, V
Seong, H
Rothery, S
Korchev, Y
Shevchuk, A
Stevens, MM
Item Type: Journal Article
Abstract: Owing to their ability to efficiently deliver biological cargo and sense the intracellular milieu, vertical arrays of high aspect ratio nanostructures, known as nanoneedles, are being developed as minimally invasive tools for cell manipulation. However, little is known of the mechanisms of cargo transfer across the cell membrane‐nanoneedle interface. In particular, the contributions of membrane piercing, modulation of membrane permeability and endocytosis to cargo transfer remain largely unexplored. Here, combining state‐of‐the‐art electron and scanning ion conductance microscopy with molecular biology techniques, it is shown that porous silicon nanoneedle arrays concurrently stimulate independent endocytic pathways which contribute to enhanced biomolecule delivery into human mesenchymal stem cells. Electron microscopy of the cell membrane at nanoneedle sites shows an intact lipid bilayer, accompanied by an accumulation of clathrin‐coated pits and caveolae. Nanoneedles enhance the internalization of biomolecular markers of endocytosis, highlighting the concurrent activation of caveolae‐ and clathrin‐mediated endocytosis, alongside macropinocytosis. These events contribute to the nanoneedle‐mediated delivery (nanoinjection) of nucleic acids into human stem cells, which distribute across the cytosol and the endolysosomal system. This data extends the understanding of how nanoneedles modulate biological processes to mediate interaction with the intracellular space, providing indications for the rational design of improved cell‐manipulation technologies.
Issue Date: 22-Mar-2019
Date of Acceptance: 11-Jan-2019
URI: http://hdl.handle.net/10044/1/67112
DOI: https://dx.doi.org/10.1002/adma.201806788
ISSN: 0935-9648
Publisher: Wiley
Journal / Book Title: Advanced Materials
Volume: 31
Issue: 12
Copyright Statement: © 2019 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim. This is the pre-peer reviewed version of the following article, which has been published in final form at https://onlinelibrary.wiley.com/doi/full/10.1002/adma.201806788
Sponsor/Funder: Commission of the European Communities
Wellcome Trust
Engineering & Physical Science Research Council (EPSRC)
Research Council of Norway
Biotechnology and Biological Sciences Research Council (BBSRC)
Funder's Grant Number: 676137
098411/Z/12/Z
EP/K020641/1
'Ref: 512010/144566 - SFF-HTH
BB/M022080/1
Keywords: Science & Technology
Physical Sciences
Technology
Chemistry, Multidisciplinary
Chemistry, Physical
Nanoscience & Nanotechnology
Materials Science, Multidisciplinary
Physics, Applied
Physics, Condensed Matter
Chemistry
Science & Technology - Other Topics
Materials Science
Physics
biointerface
drug delivery
endocytosis
nanoneedles
porous silicon
ION CONDUCTANCE MICROSCOPY
INTRACELLULAR DELIVERY
MEMBRANE CURVATURE
CELLS
INTEGRATION
NANOWIRES
PLATFORM
SYSTEM
ARRAYS
PROBES
biointerface
drug delivery
endocytosis
nanoneedles
porous silicon
02 Physical Sciences
03 Chemical Sciences
09 Engineering
Nanoscience & Nanotechnology
Publication Status: Published
Embargo Date: 2020-01-24
Article Number: ARTN 1806788
Online Publication Date: 2019-01-24
Appears in Collections:Faculty of Engineering
Materials
National Heart and Lung Institute
Faculty of Medicine
Faculty of Natural Sciences



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