Quantification of vaporized targeted nanodroplets using high-frame-rate ultrasound and optics
File(s)
Accepted version
Author(s)
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. Particularly,the contributions of membrane piercing, modulation of membrane permeability and endocytosis to cargo transfer remain largelyunexplored. Here, combining state-of-the-art electron and scanning ion conductance microscopy with molecular biology techniques, we show 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 internalisation 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.
Date Issued
2019-05
Date Acceptance
2019-01-11
Citation
Ultrasound in Medicine and Biology, 2019, 45 (5), pp.1131-1142
ISSN
0301-5629
Publisher
Elsevier
Start Page
1131
End Page
1142
Journal / Book Title
Ultrasound in Medicine and Biology
Volume
45
Issue
5
Copyright Statement
Copyright©2019 World Federation for Ultrasound in Medicine & Biology. All rights reserved. Published version: https://doi.org/10.1016/j.ultrasmedbio.2019.01.009 . Author's post-print version released with a Creative Commons Attribution Non-Commercial No Derivatives License https://creativecommons.org/licenses/by-nc-nd/4.0/ .
Subjects
Science & Technology
Technology
Life Sciences & Biomedicine
Acoustics
Radiology, Nuclear Medicine & Medical Imaging
Targeted molecular imaging
Nanodroplets
Phase-change contrast agents
Microbubbles
CHANGE CONTRAST AGENTS
ACOUSTIC DROPLET VAPORIZATION
PHASE-II
IN-VITRO
CANCER
DELIVERY
VINTAFOLIDE
COMBINATION
DOXORUBICIN
ACTIVATION
Microbubbles
Nanodroplets
Phase-change contrast agents
Targeted molecular imaging
Acoustics
1103 Clinical Sciences
Publication Status
Published
Date Publish Online
2019-02-28