Influence of nanoparticle shapes on cellular uptake of paclitaxel loaded nanoparticles in 2D and 3D cancer models

Zhao, J; Lu, H; Wong, S; Lu, M; Xiao, P; Stenzel, MH

Influence of nanoparticle shapes on cellular uptake of paclitaxel loaded nanoparticles in 2D and 3D cancer models

Zhao, J Lu, H

Wong, S Lu, M Xiao, P Stenzel, MH

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Publisher:: ROYAL SOC CHEMISTRY
Publication Type:: Journal Article
Citation:: Polymer Chemistry, 2017, 8, (21), pp. 3317-3326
Issue Date:: 2017

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Field	Value	Language
dc.contributor.author	Zhao, J
dc.contributor.author	Lu, H https://orcid.org/0000-0001-6932-1900
dc.contributor.author	Wong, S
dc.contributor.author	Lu, M
dc.contributor.author	Xiao, P
dc.contributor.author	Stenzel, MH
dc.date.accessioned	2022-10-03T20:55:24Z
dc.date.available	2022-10-03T20:55:24Z
dc.date.issued	2017
dc.identifier.citation	Polymer Chemistry, 2017, 8, (21), pp. 3317-3326
dc.identifier.issn	1759-9954
dc.identifier.issn	1759-9962
dc.identifier.uri	http://hdl.handle.net/10453/162249
dc.description.abstract	Enhanced cellular uptake and efficient penetration of nanocarriers inside tumors is paramount to successful anti-cancer therapy. While many studies have shown the important role nanoparticle shape plays in cellular uptake, no detailed conclusions on the most efficient drug carrier shape have been drawn at this stage. Here, a series of fructose-based amphiphilic block copolymers poly(1-O-MAFru)-b-PMMA are synthesized via RAFT polymerization. Three different morphologies (spheres, rods and vesicles) are prepared by self-assembly under different processing conditions. The shape effects of fructose-coated nanoparticles on cellular uptake by two breast cancer cell lines (MCF-7 cells and MDA-MB-231 cells) in 2D and 3D cell culture models are investigated. The cytotoxicity of corresponding paclitaxel-loaded nanoparticles are tested as well to give a comprehensive comparison between cellular uptake and resulting therapeutic efficacy after drug encapsulation in both cell culture models. Consistent results in 2D models confirm the shape effect of nanoparticles on cellular uptake. Unexpectedly, the shape does influence significantly the cell growth inhibition in 3D multicellular spheroids due to the possible cessation of transcellular delivery of nanoparticles in the apoptotic peripheral cells, caused by faster release of drugs from un-crosslinked micelles. Our results confirm the shape effect of nanoparticles on 2D models can vary from 3D models due to parameters such as spheroid penetration that can now play a pivotal role.
dc.language	English
dc.publisher	ROYAL SOC CHEMISTRY
dc.relation.ispartof	Polymer Chemistry
dc.relation.isbasedon	10.1039/c7py00385d
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	0303 Macromolecular and Materials Chemistry, 0307 Theoretical and Computational Chemistry
dc.title	Influence of nanoparticle shapes on cellular uptake of paclitaxel loaded nanoparticles in 2D and 3D cancer models
dc.type	Journal Article
utslib.citation.volume	8
utslib.for	0303 Macromolecular and Materials Chemistry
utslib.for	0307 Theoretical and Computational Chemistry
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
pubs.organisational-group	/University of Technology Sydney/Strength - IBMD - Initiative for Biomedical Devices
utslib.copyright.status	closed_access	*
dc.date.updated	2022-10-03T20:55:22Z
pubs.issue	21
pubs.publication-status	Published
pubs.volume	8
utslib.citation.issue	21

Abstract:

Enhanced cellular uptake and efficient penetration of nanocarriers inside tumors is paramount to successful anti-cancer therapy. While many studies have shown the important role nanoparticle shape plays in cellular uptake, no detailed conclusions on the most efficient drug carrier shape have been drawn at this stage. Here, a series of fructose-based amphiphilic block copolymers poly(1-O-MAFru)-b-PMMA are synthesized via RAFT polymerization. Three different morphologies (spheres, rods and vesicles) are prepared by self-assembly under different processing conditions. The shape effects of fructose-coated nanoparticles on cellular uptake by two breast cancer cell lines (MCF-7 cells and MDA-MB-231 cells) in 2D and 3D cell culture models are investigated. The cytotoxicity of corresponding paclitaxel-loaded nanoparticles are tested as well to give a comprehensive comparison between cellular uptake and resulting therapeutic efficacy after drug encapsulation in both cell culture models. Consistent results in 2D models confirm the shape effect of nanoparticles on cellular uptake. Unexpectedly, the shape does influence significantly the cell growth inhibition in 3D multicellular spheroids due to the possible cessation of transcellular delivery of nanoparticles in the apoptotic peripheral cells, caused by faster release of drugs from un-crosslinked micelles. Our results confirm the shape effect of nanoparticles on 2D models can vary from 3D models due to parameters such as spheroid penetration that can now play a pivotal role.

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http://hdl.handle.net/10453/162249