Bone-targeting dendrimer for the delivery of methotrexate and treatment of bone metastasis.

We developed a bone-targeting dendrimer for the delivery of anti-tumour agents and effective treatment of bone metastasis, in which alendronate (ALN), a bone-targeting moiety, is covalently bonded to a polyethylene glycol (PEG)-conjugated polyamidoamine (PAMAM) dendrimer (PEG-PAMAM-ALN). Approximately 7.0 and 21.9% of the administered doses of [111 In]PAMAM and PEG-PAMAM-ALN accumulated in the bones within 180 min after intravenous injection in mice, respectively. [3 H]-labelled methotrexate (MTX) rapidly disappeared from the blood, and bone distribution was found to be only 1.1% of the administered dose at 180 min. In contrast, 21.5% of the administered dose of [3 H]MTX-loaded PEG-PAMAM-ALN accumulated in the bones at 180 min after intravenous injection in mice, which was approximately 20-fold higher than that of [3 H]MTX. In a bone metastatic tumour mouse model, in which B16-BL6/Luc cells were injected into the left ventricle of female C57BL/6 mice, the growth of metastatic tumour in the bones was significantly inhibited by intravenous injection of MTX-loaded PEG-PAMAM-ALN. These findings indicate that PEG-PAMAM-ALN is a promising bone-targeting carrier for the delivery of anti-tumour agents and treatment of bone metastasis.