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

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.