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

Diego dos Santos Ferreira, Bruno Luís Jesus de Oliveira Pinto, Vidhya Kumar, Valbert Nascimento Cardoso, Simone Odília Fernandes, Cristina Maria Souza, Geovanni Dantas Cassali, Anna Moore, David E. Sosnovik, Christian T. Farrar, Elaine Amaral Leite, Ricardo José Alves, Mônica Cristina de Oliveira, Alexander Guimaraes, Peter Caravan

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1693-1701
Number of pages9
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume13
Issue number5
DOIs
StatePublished - Jul 1 2017

Keywords

  • Bisphosphonates
  • Bone tumor
  • Cardiotoxicity
  • Doxorubicin
  • Hydroxyapatite-targeting

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Bioengineering
  • Biomedical Engineering
  • Molecular Medicine
  • Materials Science(all)
  • Pharmaceutical Science

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    dos Santos Ferreira, D., Jesus de Oliveira Pinto, B. L., Kumar, V., Cardoso, V. N., Fernandes, S. O., Souza, C. M., Cassali, G. D., Moore, A., Sosnovik, D. E., Farrar, C. T., Leite, E. A., Alves, R. J., de Oliveira, M. C., Guimaraes, A., & Caravan, P. (2017). Evaluation of antitumor activity and cardiac toxicity of a bone-targeted ph-sensitive liposomal formulation in a bone metastasis tumor model in mice. Nanomedicine: Nanotechnology, Biology, and Medicine, 13(5), 1693-1701. https://doi.org/10.1016/j.nano.2017.03.005