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Evaluation of antitumor activity and cardiac toxicity of a bone-targeted ph-sensitive liposomal formulation in a bone metastasis tumor model in mice

2017; Elsevier BV; Volume: 13; Issue: 5 Linguagem: Inglês

10.1016/j.nano.2017.03.005

1549-9642

Diêgo S. Ferreira, Bruno L. Oliveira, Vidhya Kumar, Valbert Nascimento Cardoso, Simone Odília Antunes Fernandes, Cristina Maria de Souza, Geovanni Dantas Cassali, Anna Moore, David E. Sosnovik, Christian T. Farrar, Elaine Amaral Leite, Ricardo José Alves, Mônica Cristina Oliveira, Alexander R. Guimarães, Peter Caravan,

Medical Imaging and Pathology Studies

Chemotherapy for bone tumors is a major challenge because of the inability of therapeutics to penetrate dense bone mineral. We hypothesize that a nanostructured formulation with high affinity for bone could deliver drug to the tumor while minimizing off-target toxicity. Here, we evaluated the efficacy and toxicity of a novel bone-targeted, pH-sensitive liposomal formulation containing doxorubicin in an animal model of bone metastasis. Biodistribution studies with the liposome showed good uptake in tumor, but low accumulation of doxorubicin in the heart. Mice treated with the bone-targeted liposome formulation showed a 70% reduction in tumor volume, compared to 35% reduction for free doxorubicin at the same dose. Both cardiac toxicity and overall mortality were significantly lower for animals treated with the bone-targeted liposomes compared to free drug. Bone-targeted, pH-sensitive, doxorubicin containing liposomes represent a promising approach to selectively delivering doxorubicin to bone tumors while minimizing cardiac toxicity.