Nanoparticles Based on Star Polymers as Theranostic Vectors: Endosomal-Triggered Drug Release Combined with MRI Sensitivity

Dual-functional star polymers (diameters 15 nm) are synthesized producing nanoparticles with excellent colloidal stability in both water and serum. The nanoparticles are built with aldehyde groups in the core and activated esters in the arms. The different reactivity of the two functional groups to...

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Main Authors: Li, Y., Duong, H., Laurent, S., MacMillan, A., Whan, R., Elst, L., Muller, R., Hu, J., Lowe, Andrew, Boyer, C., Davis, T.
Format: Journal Article
Published: Wiley - V C H Verlag GmbH & Co. KGaA 2015
Online Access:http://hdl.handle.net/20.500.11937/11485
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author Li, Y.
Duong, H.
Laurent, S.
MacMillan, A.
Whan, R.
Elst, L.
Muller, R.
Hu, J.
Lowe, Andrew
Boyer, C.
Davis, T.
author_facet Li, Y.
Duong, H.
Laurent, S.
MacMillan, A.
Whan, R.
Elst, L.
Muller, R.
Hu, J.
Lowe, Andrew
Boyer, C.
Davis, T.
author_sort Li, Y.
building Curtin Institutional Repository
collection Online Access
description Dual-functional star polymers (diameters 15 nm) are synthesized producing nanoparticles with excellent colloidal stability in both water and serum. The nanoparticles are built with aldehyde groups in the core and activated esters in the arms. The different reactivity of the two functional groups to sequentially react with different amino compounds is exploited; doxorubicin (DOX) and 1-(5-amino-3-aza-2-oxypentyl)-4,7,10-tris(tert-butoxycarbonylmethyl)-1,4,7,10-tetraazacyclododecane (DO3A-tBu-NH2)—a chelating agent effective for the complexation of Gadolinium ions (Gd). The activated ester group is employed to attach the DO3A chelating agent, while the aldehyde groups are exploited for DOX conjugation, providing a controlled release mechanism for DOX in acidic environments. DOX/Gd-loaded nanoparticles are rapidly taken up by MCF-7 breast cancer cells, subsequently releasing DOX as demonstrated using in vitro fluorescence lifetime imaging microscopy (FLIM). Endosomal, DOX release is observed, using a phasor plot representation of the fluorescence lifetime data, showing an increase of native DOX with time. The MRI properties of the stars are assessed and the relaxivity of Gd loaded in stars is three times higher than conventional organic Gd/DO3A complexes. The DOX/Gd-conjugated nanoparticles yield a similar IC50 to native DOX for breast cancer cell lines, confirming that DOX integrity is conserved during nanoparticle attachment and release.
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institution Curtin University Malaysia
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publisher Wiley - V C H Verlag GmbH & Co. KGaA
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spelling curtin-20.500.11937-114852017-09-13T14:53:18Z Nanoparticles Based on Star Polymers as Theranostic Vectors: Endosomal-Triggered Drug Release Combined with MRI Sensitivity Li, Y. Duong, H. Laurent, S. MacMillan, A. Whan, R. Elst, L. Muller, R. Hu, J. Lowe, Andrew Boyer, C. Davis, T. Dual-functional star polymers (diameters 15 nm) are synthesized producing nanoparticles with excellent colloidal stability in both water and serum. The nanoparticles are built with aldehyde groups in the core and activated esters in the arms. The different reactivity of the two functional groups to sequentially react with different amino compounds is exploited; doxorubicin (DOX) and 1-(5-amino-3-aza-2-oxypentyl)-4,7,10-tris(tert-butoxycarbonylmethyl)-1,4,7,10-tetraazacyclododecane (DO3A-tBu-NH2)—a chelating agent effective for the complexation of Gadolinium ions (Gd). The activated ester group is employed to attach the DO3A chelating agent, while the aldehyde groups are exploited for DOX conjugation, providing a controlled release mechanism for DOX in acidic environments. DOX/Gd-loaded nanoparticles are rapidly taken up by MCF-7 breast cancer cells, subsequently releasing DOX as demonstrated using in vitro fluorescence lifetime imaging microscopy (FLIM). Endosomal, DOX release is observed, using a phasor plot representation of the fluorescence lifetime data, showing an increase of native DOX with time. The MRI properties of the stars are assessed and the relaxivity of Gd loaded in stars is three times higher than conventional organic Gd/DO3A complexes. The DOX/Gd-conjugated nanoparticles yield a similar IC50 to native DOX for breast cancer cell lines, confirming that DOX integrity is conserved during nanoparticle attachment and release. 2015 Journal Article http://hdl.handle.net/20.500.11937/11485 10.1002/adhm.201400164 Wiley - V C H Verlag GmbH & Co. KGaA restricted
spellingShingle Li, Y.
Duong, H.
Laurent, S.
MacMillan, A.
Whan, R.
Elst, L.
Muller, R.
Hu, J.
Lowe, Andrew
Boyer, C.
Davis, T.
Nanoparticles Based on Star Polymers as Theranostic Vectors: Endosomal-Triggered Drug Release Combined with MRI Sensitivity
title Nanoparticles Based on Star Polymers as Theranostic Vectors: Endosomal-Triggered Drug Release Combined with MRI Sensitivity
title_full Nanoparticles Based on Star Polymers as Theranostic Vectors: Endosomal-Triggered Drug Release Combined with MRI Sensitivity
title_fullStr Nanoparticles Based on Star Polymers as Theranostic Vectors: Endosomal-Triggered Drug Release Combined with MRI Sensitivity
title_full_unstemmed Nanoparticles Based on Star Polymers as Theranostic Vectors: Endosomal-Triggered Drug Release Combined with MRI Sensitivity
title_short Nanoparticles Based on Star Polymers as Theranostic Vectors: Endosomal-Triggered Drug Release Combined with MRI Sensitivity
title_sort nanoparticles based on star polymers as theranostic vectors: endosomal-triggered drug release combined with mri sensitivity
url http://hdl.handle.net/20.500.11937/11485