Journal
ADVANCED MATERIALS
Volume 31, Issue 12, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.201806788
Keywords
biointerface; drug delivery; endocytosis; nanoneedles; porous silicon
Categories
Funding
- Department of Medicine
- Department of Bioengineering, Imperial College London
- European Research Council [ERC StG 759577]
- Royal Society Newton International Fellowship
- European Framework Programme 7 Marie Curie Actions [302638]
- National Research Foundation of Korea (NRF) - Ministry of Education [2017R1A6A3A03007397]
- Rosetrees Trust
- Stoneygate Trust
- Bloom Foundation
- Robert Luff Foundation
- Wellcome Trust [098411/Z/12/Z]
- Research Council of Norway through its Centres of Excellence scheme [262613]
- Engineering and Physical Science Research Council (EPSRC) [EP/K020641/1]
- NanoMed Marie Sklodowska-Curie ITN from the H2020 program [676137]
- National Research Foundation of Korea [2017R1A6A3A03007397] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- BBSRC [BB/M022080/1, BB/L005816/1, BB/D020875/1] Funding Source: UKRI
- EPSRC [EP/K020641/1, EP/P011985/1] Funding Source: UKRI
- MRC [MC_PC_16048] Funding Source: UKRI
- Marie Curie Actions (MSCA) [676137] Funding Source: Marie Curie Actions (MSCA)
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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.
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