Dendrimer-based macromolecular conjugate for the kidney-directed delivery of a multitargeted sunitinib analogue

M. E.Emmy M. Dolman; Kim M.A. van Dorenmalen; Ebel H.E. Pieters; Rolf W. Sparidans; Marie Lacombe; Bálint Szokol; László Orfi; György Kéri; Niels Bovenschen; Gert Storm; Wim E. Hennink; Robbert J. Kok

doi:10.1002/mabi.201100277

Dendrimer-based macromolecular conjugate for the kidney-directed delivery of a multitargeted sunitinib analogue

M. E.Emmy M. Dolman
, Kim M.A. van Dorenmalen
, Ebel H.E. Pieters
, Rolf W. Sparidans
, Marie Lacombe
, Bálint Szokol
, László Orfi
, György Kéri
, Niels Bovenschen
, Gert Storm
, Wim E. Hennink
, Robbert J. Kok

Onderzoeksoutput: Bijdrage aan tijdschrift › Artikel › peer review

21 Citaten (Scopus)

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The development of a macromolecular conjugate of a multitargeted tyrosine kinase inhibitor is described that can be used for renal-specific delivery into proximal tubular cells. A novel sunitinib analogue, that is, 17864, is conjugated to a NH ₂-PAMAM-G3 dendrimer via the platinum (II)-based Universal Linkage System (ULS™). The activity of 17864 is retained after coordination to the ULS linker alone or when coupled to NH ₂-PAMAM-G3. 17864-UlS-NH ₂-PAMAM-G3 is non-toxic to proximal tubular cells in vitro. After intravenous administration to mice, 17864-UlS-NH ₂-PAMAM-G3 rapidly and efficiently accumulates in the kidneys. These results are encouraging for future studies focusing on the development of novel therapeutics for the treatment of renal diseases.

Originele taal-2	Engels
Pagina's (van-tot)	93-103
Aantal pagina's	11
Tijdschrift	Macromolecular Bioscience
Volume	12
Nummer van het tijdschrift	1
DOI's	https://doi.org/10.1002/mabi.201100277
Status	Gepubliceerd - jan 2012
Extern gepubliceerd	Ja

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10.1002/mabi.201100277

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Dolman, M. E. E. M., van Dorenmalen, K. M. A., Pieters, E. H. E., Sparidans, R. W., Lacombe, M., Szokol, B., Orfi, L., Kéri, G., Bovenschen, N., Storm, G., Hennink, W. E., & Kok, R. J. (2012). Dendrimer-based macromolecular conjugate for the kidney-directed delivery of a multitargeted sunitinib analogue. Macromolecular Bioscience, 12(1), 93-103. https://doi.org/10.1002/mabi.201100277

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title = "Dendrimer-based macromolecular conjugate for the kidney-directed delivery of a multitargeted sunitinib analogue",

abstract = "The development of a macromolecular conjugate of a multitargeted tyrosine kinase inhibitor is described that can be used for renal-specific delivery into proximal tubular cells. A novel sunitinib analogue, that is, 17864, is conjugated to a NH 2-PAMAM-G3 dendrimer via the platinum (II)-based Universal Linkage System (ULS{\texttrademark}). The activity of 17864 is retained after coordination to the ULS linker alone or when coupled to NH 2-PAMAM-G3. 17864-UlS-NH 2-PAMAM-G3 is non-toxic to proximal tubular cells in vitro. After intravenous administration to mice, 17864-UlS-NH 2-PAMAM-G3 rapidly and efficiently accumulates in the kidneys. These results are encouraging for future studies focusing on the development of novel therapeutics for the treatment of renal diseases.",

keywords = "Dendrimers, Drug delivery systems, Kidney, Platinum linkers, Sunitinib",

author = "Dolman, \{M. E.Emmy M.\} and \{van Dorenmalen\}, \{Kim M.A.\} and Pieters, \{Ebel H.E.\} and Sparidans, \{Rolf W.\} and Marie Lacombe and B{\'a}lint Szokol and L{\'a}szl{\'o} Orfi and Gy{\"o}rgy K{\'e}ri and Niels Bovenschen and Gert Storm and Hennink, \{Wim E.\} and Kok, \{Robbert J.\}",

year = "2012",

month = jan,

doi = "10.1002/mabi.201100277",

language = "English",

volume = "12",

pages = "93--103",

journal = "Macromolecular Bioscience",

issn = "1616-5187",

publisher = "Wiley-VCH Verlag",

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AU - Dolman, M. E.Emmy M.

AU - van Dorenmalen, Kim M.A.

AU - Pieters, Ebel H.E.

AU - Sparidans, Rolf W.

AU - Lacombe, Marie

AU - Szokol, Bálint

AU - Orfi, László

AU - Kéri, György

AU - Bovenschen, Niels

AU - Storm, Gert

AU - Hennink, Wim E.

AU - Kok, Robbert J.

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AB - The development of a macromolecular conjugate of a multitargeted tyrosine kinase inhibitor is described that can be used for renal-specific delivery into proximal tubular cells. A novel sunitinib analogue, that is, 17864, is conjugated to a NH 2-PAMAM-G3 dendrimer via the platinum (II)-based Universal Linkage System (ULS™). The activity of 17864 is retained after coordination to the ULS linker alone or when coupled to NH 2-PAMAM-G3. 17864-UlS-NH 2-PAMAM-G3 is non-toxic to proximal tubular cells in vitro. After intravenous administration to mice, 17864-UlS-NH 2-PAMAM-G3 rapidly and efficiently accumulates in the kidneys. These results are encouraging for future studies focusing on the development of novel therapeutics for the treatment of renal diseases.

KW - Dendrimers

KW - Drug delivery systems

KW - Kidney

KW - Platinum linkers

KW - Sunitinib

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DO - 10.1002/mabi.201100277

M3 - Article

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AN - SCOPUS:84855443297

SN - 1616-5187

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EP - 103

JO - Macromolecular Bioscience

JF - Macromolecular Bioscience

IS - 1

ER -

Dendrimer-based macromolecular conjugate for the kidney-directed delivery of a multitargeted sunitinib analogue

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