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Probing the effect of rigidity on the cellular uptake of core-shell nanoparticles : stiffness effects are size dependent

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Gurnani, Pratik, Sanchez-Cano, Carlos, Xandri-Monje, Helena, Zhang, Junliang, Ellacott, Sean H., Mansfield, Edward D. H., Hartlieb, Matthias, Dallmann, Robert and Perrier, Sébastien (2022) Probing the effect of rigidity on the cellular uptake of core-shell nanoparticles : stiffness effects are size dependent. Small, 18 (38). 2203070. doi:10.1002/smll.202203070 ISSN 1613-6810.

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Official URL: https://doi.org/10.1002/smll.202203070

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Abstract

Nanoparticles are well established vectors for the delivery of a wide range of biomedically relevant cargoes. Numerous studies have investigated the impact of size, shape, charge, and surface functionality of nanoparticles on mammalian cellular uptake. Rigidity has been studied to a far lesser extent, and its effects are still unclear. Here, the importance of this property, and its interplay with particle size, is systematically explored using a library of core-shell spherical PEGylated nanoparticles synthesized by RAFT emulsion polymerization. Rigidity of these particles is controlled by altering the intrinsic glass transition temperature of their constituting polymers. Three polymeric core rigidities are tested: hard, medium, and soft using two particle sizes, 50 and 100 nm diameters. Cellular uptake studies indicate that softer particles are taken up faster and threefold more than harder nanoparticles with the larger 100 nm particles. In addition, the study indicates major differences in the cellular uptake pathway, with harder particles being internalized through clathrin- and caveolae-mediated endocytosis as well as macropinocytosis, while softer particles are taken up bycaveolae- and non-receptormediated endocytosis. However, 50 nm derivatives do not show any appreciable differences in uptake efficiency, suggesting that rigidity as a parameter in the biological regime may be size dependent.

Item Type: Journal Article
Subjects: R Medicine > RS Pharmacy and materia medica
Divisions: Faculty of Science, Engineering and Medicine > Science > Chemistry
Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH): Nanoparticles, Drug delivery systems, Polymers -- Experiments -- Research
Journal or Publication Title: Small
Publisher: Wiley - V C H Verlag GmbH & Co. KGaA
ISSN: 1613-6810
Official Date: 22 September 2022
Dates:
DateEvent
22 September 2022Published
19 August 2022Available
19 August 2022Accepted
18 May 2022Submitted
Volume: 18
Number: 38
Number of Pages: 11
Article Number: 2203070
DOI: 10.1002/smll.202203070
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access (Creative Commons)
Date of first compliant deposit: 22 August 2022
Date of first compliant Open Access: 25 August 2022
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
UNSPECIFIEDUniversity of Warwickhttp://dx.doi.org/10.13039/501100000741
C53561Cancer Research UKhttp://dx.doi.org/10.13039/501100000289
A19933[EPSRC] Engineering and Physical Sciences Research Councilhttp://dx.doi.org/10.13039/501100000266
HA 7725/1-1[DFG] Deutsche Forschungsgemeinschafthttp://dx.doi.org/10.13039/501100001659
BB/M01228X/1[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
UNSPECIFIEDMonash Universityhttp://dx.doi.org/10.13039/501100001779

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