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

Research output: Contribution to journal › Article › peer-review

21 Citations (Scopus)

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™). 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.

Original language	English
Pages (from-to)	93-103
Number of pages	11
Journal	Macromolecular Bioscience
Volume	12
Issue number	1
DOIs	https://doi.org/10.1002/mabi.201100277
Publication status	Published - Jan 2012
Externally published	Yes

Keywords

Dendrimers
Drug delivery systems
Kidney
Platinum linkers
Sunitinib

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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",

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journal = "Macromolecular Bioscience",

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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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JO - Macromolecular Bioscience

JF - Macromolecular Bioscience

IS - 1

ER -

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

Abstract

Keywords

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