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 tijdschriftArtikelpeer review

17 Citaten (Scopus)

Samenvatting

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-2Engels
Pagina's (van-tot)93-103
Aantal pagina's11
TijdschriftMacromolecular Bioscience
Volume12
Nummer van het tijdschrift1
DOI's
StatusGepubliceerd - jan. 2012
Extern gepubliceerdJa

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