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

Emmy 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

Emmy 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 › Academic › peer-review

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 NH2-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 NH2-PAMAM-G3. 17864-UlS-NH2-PAMAM-G3 is non-toxic to proximal tubular cells in vitro. After intravenous administration to mice, 17864-UlS-NH2-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. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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 - 1 Jan 2012

Keywords

Dendrimers
Drug delivery systems
Kidney
Platinum linkers
Sunitinib
17864
amine terminated poly(amidoamine) G3
dendrimer
drug carrier
protein tyrosine kinase
sunitinib
sunitinib derivative
unclassified drug
animal experiment
article
controlled study
drug accumulation
drug conjugation
drug cytotoxicity
drug delivery system
drug synthesis
drug tissue level
drug uptake
enzyme inhibition
human
human cell
in vitro study
internalization
kidney
kidney proximal tubule
kidney tubule cell
male
mouse
nonhuman
single drug dose

Access to Document

10.1002/mabi.201100277

Cite this

Dolman, E., 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

@article{aee80fea1e454d0ba0625e165c111949,

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 NH2-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 NH2-PAMAM-G3. 17864-UlS-NH2-PAMAM-G3 is non-toxic to proximal tubular cells in vitro. After intravenous administration to mice, 17864-UlS-NH2-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. {\textcopyright} 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",

keywords = "Dendrimers, Drug delivery systems, Kidney, Platinum linkers, Sunitinib, 17864, amine terminated poly(amidoamine) G3, dendrimer, drug carrier, protein tyrosine kinase, sunitinib, sunitinib derivative, unclassified drug, animal experiment, article, controlled study, drug accumulation, drug conjugation, drug cytotoxicity, drug delivery system, drug synthesis, drug tissue level, drug uptake, enzyme inhibition, human, human cell, in vitro study, internalization, kidney, kidney proximal tubule, kidney tubule cell, male, mouse, nonhuman, single drug dose",

author = "Emmy Dolman 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,

day = "1",

doi = "10.1002/mabi.201100277",

language = "English",

volume = "12",

pages = "93--103",

journal = "Macromolecular Bioscience",

issn = "1616-5187",

publisher = "Wiley-VCH Verlag",

number = "1",

}

TY - JOUR

T1 - Dendrimer-based macromolecular conjugate for the kidney-directed delivery of a multitargeted sunitinib analogue

AU - Dolman, Emmy

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.

PY - 2012/1/1

Y1 - 2012/1/1

N2 - 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 NH2-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 NH2-PAMAM-G3. 17864-UlS-NH2-PAMAM-G3 is non-toxic to proximal tubular cells in vitro. After intravenous administration to mice, 17864-UlS-NH2-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. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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 NH2-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 NH2-PAMAM-G3. 17864-UlS-NH2-PAMAM-G3 is non-toxic to proximal tubular cells in vitro. After intravenous administration to mice, 17864-UlS-NH2-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. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

KW - Dendrimers

KW - Drug delivery systems

KW - Kidney

KW - Platinum linkers

KW - Sunitinib

KW - 17864

KW - amine terminated poly(amidoamine) G3

KW - dendrimer

KW - drug carrier

KW - protein tyrosine kinase

KW - sunitinib

KW - sunitinib derivative

KW - unclassified drug

KW - animal experiment

KW - article

KW - controlled study

KW - drug accumulation

KW - drug conjugation

KW - drug cytotoxicity

KW - drug delivery system

KW - drug synthesis

KW - drug tissue level

KW - drug uptake

KW - enzyme inhibition

KW - human

KW - human cell

KW - in vitro study

KW - internalization

KW - kidney

KW - kidney proximal tubule

KW - kidney tubule cell

KW - male

KW - mouse

KW - nonhuman

KW - single drug dose

U2 - 10.1002/mabi.201100277

DO - 10.1002/mabi.201100277

M3 - Article

SN - 1616-5187

VL - 12

SP - 93

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

Abstract

Keywords

Access to Document

Fingerprint

Cite this