Influence of PEGylation and RGD loading on the targeting properties of radiolabeled liposomal nanoparticles

Christine Rangger,1 Anna Helbok,1 Elisabeth von Guggenberg,1 Jane Sosabowski,2 Thorsten Radolf,3 Ruth Prassl,4 Fritz Andreae,3 Gudrun C Thurner,5 Roland Haubner,1 Clemens Decristoforo11Department of Nuclear Medicine, Innsbruck Medical University, Innsbruck, Austria; 2Center for Molecular Oncology, B...

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Autores principales:	Rangger C, Helbok A, von Guggenberg E, Sosabowski J, Radolf T, Prassl R, Andreae F, Thurner GC, Haubner R, Decristoforo C
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Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/a1340052aa2845cf819c9c9c907822e7
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spelling	oai:doaj.org-article:a1340052aa2845cf819c9c9c907822e72021-12-02T02:34:13ZInfluence of PEGylation and RGD loading on the targeting properties of radiolabeled liposomal nanoparticles1176-91141178-2013https://doaj.org/article/a1340052aa2845cf819c9c9c907822e72012-11-01T00:00:00Zhttp://www.dovepress.com/influence-of-pegylation-and-rgd-loading-on-the-targeting-properties-of-a11617https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Christine Rangger,1 Anna Helbok,1 Elisabeth von Guggenberg,1 Jane Sosabowski,2 Thorsten Radolf,3 Ruth Prassl,4 Fritz Andreae,3 Gudrun C Thurner,5 Roland Haubner,1 Clemens Decristoforo11Department of Nuclear Medicine, Innsbruck Medical University, Innsbruck, Austria; 2Center for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK; 3piCHEM Research and Development, Graz, 4Institute of Biophysics and Nanosystems Research, Austrian Academy of Sciences, Graz, 5Department of Radiology, Innsbruck Medical University, Innsbruck, AustriaPurpose: Liposomes have been proposed to be a means of selectively targeting cancer sites for diagnostic and therapeutic applications. The focus of this work was the evaluation of radiolabeled PEGylated liposomes derivatized with varying amounts of a cyclic arginyl&ndash;glycyl&ndash;aspartic acid (RGD) peptide. RGD peptides are known to bind to &alpha;v&beta;3 integrin receptors overexpressed during tumor-induced angiogenesis.Methods: Several liposomal nanoparticles carrying the RGD peptide targeting sequence (RLPs) were synthesized using a combination of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, cholesterol, diethylenetriaminepentaacetic acid-derivatized lipids for radiolabeling, a polyethylene glycol (PEG) building block, and a lipid-based RGD building block. Relative amounts of RGD and PEG building blocks were varied. In vitro binding affinities were determined using isolated &alpha;v&beta;3 integrin receptors incubated with different concentrations of RLPs in competition with iodine-125-labeled cyclo-(-RGDyV-). Binding of the indium-111-labeled RLPs was also evaluated. Biodistribution and micro single photon emission computed tomography/computed tomography imaging studies were performed in nude mice using different tumor xenograft models.Results: RLPs were labeled with indium-111 with high radiochemical yields. In vitro binding studies of RLPs with different RGD/PEG loading revealed good binding to isolated receptors, which was dependent on the extent of RGD and PEG loading. Binding increased with higher RGD loading, whereas reduced binding was found with higher PEG loading. Biodistribution showed increased circulating time for PEGylated RLPs, but no dependence on RGD loading. Both biodistribution and micro single photon emission computed tomography/computed tomography imaging studies revealed low, nonspecific tumor uptake values.Conclusion: In this study, RLPs for targeting angiogenesis were described. Even though good binding to &alpha;v&beta;3 integrin receptors was found in vitro, the balance between PEGylation and RGD loading clearly requires optimization to achieve targeting in vivo. These data form the basis for future development and provide a platform for the investigation of multimodal approaches.Keywords: liposomes, RGD peptides, &alpha;v&beta;3 integrin receptors, angiogenesis, tumor targetingRangger CHelbok Avon Guggenberg ESosabowski JRadolf TPrassl RAndreae FThurner GCHaubner RDecristoforo CDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 5889-5900 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Rangger C Helbok A von Guggenberg E Sosabowski J Radolf T Prassl R Andreae F Thurner GC Haubner R Decristoforo C Influence of PEGylation and RGD loading on the targeting properties of radiolabeled liposomal nanoparticles
description	Christine Rangger,1 Anna Helbok,1 Elisabeth von Guggenberg,1 Jane Sosabowski,2 Thorsten Radolf,3 Ruth Prassl,4 Fritz Andreae,3 Gudrun C Thurner,5 Roland Haubner,1 Clemens Decristoforo11Department of Nuclear Medicine, Innsbruck Medical University, Innsbruck, Austria; 2Center for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK; 3piCHEM Research and Development, Graz, 4Institute of Biophysics and Nanosystems Research, Austrian Academy of Sciences, Graz, 5Department of Radiology, Innsbruck Medical University, Innsbruck, AustriaPurpose: Liposomes have been proposed to be a means of selectively targeting cancer sites for diagnostic and therapeutic applications. The focus of this work was the evaluation of radiolabeled PEGylated liposomes derivatized with varying amounts of a cyclic arginyl&ndash;glycyl&ndash;aspartic acid (RGD) peptide. RGD peptides are known to bind to &alpha;v&beta;3 integrin receptors overexpressed during tumor-induced angiogenesis.Methods: Several liposomal nanoparticles carrying the RGD peptide targeting sequence (RLPs) were synthesized using a combination of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, cholesterol, diethylenetriaminepentaacetic acid-derivatized lipids for radiolabeling, a polyethylene glycol (PEG) building block, and a lipid-based RGD building block. Relative amounts of RGD and PEG building blocks were varied. In vitro binding affinities were determined using isolated &alpha;v&beta;3 integrin receptors incubated with different concentrations of RLPs in competition with iodine-125-labeled cyclo-(-RGDyV-). Binding of the indium-111-labeled RLPs was also evaluated. Biodistribution and micro single photon emission computed tomography/computed tomography imaging studies were performed in nude mice using different tumor xenograft models.Results: RLPs were labeled with indium-111 with high radiochemical yields. In vitro binding studies of RLPs with different RGD/PEG loading revealed good binding to isolated receptors, which was dependent on the extent of RGD and PEG loading. Binding increased with higher RGD loading, whereas reduced binding was found with higher PEG loading. Biodistribution showed increased circulating time for PEGylated RLPs, but no dependence on RGD loading. Both biodistribution and micro single photon emission computed tomography/computed tomography imaging studies revealed low, nonspecific tumor uptake values.Conclusion: In this study, RLPs for targeting angiogenesis were described. Even though good binding to &alpha;v&beta;3 integrin receptors was found in vitro, the balance between PEGylation and RGD loading clearly requires optimization to achieve targeting in vivo. These data form the basis for future development and provide a platform for the investigation of multimodal approaches.Keywords: liposomes, RGD peptides, &alpha;v&beta;3 integrin receptors, angiogenesis, tumor targeting
format	article
author	Rangger C Helbok A von Guggenberg E Sosabowski J Radolf T Prassl R Andreae F Thurner GC Haubner R Decristoforo C
author_facet	Rangger C Helbok A von Guggenberg E Sosabowski J Radolf T Prassl R Andreae F Thurner GC Haubner R Decristoforo C
author_sort	Rangger C
title	Influence of PEGylation and RGD loading on the targeting properties of radiolabeled liposomal nanoparticles
title_short	Influence of PEGylation and RGD loading on the targeting properties of radiolabeled liposomal nanoparticles
title_full	Influence of PEGylation and RGD loading on the targeting properties of radiolabeled liposomal nanoparticles
title_fullStr	Influence of PEGylation and RGD loading on the targeting properties of radiolabeled liposomal nanoparticles
title_full_unstemmed	Influence of PEGylation and RGD loading on the targeting properties of radiolabeled liposomal nanoparticles
title_sort	influence of pegylation and rgd loading on the targeting properties of radiolabeled liposomal nanoparticles
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/a1340052aa2845cf819c9c9c907822e7
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Influence of PEGylation and RGD loading on the targeting properties of radiolabeled liposomal nanoparticles

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