TY - JOUR
T1 - Evaluation of antitumor activity and cardiac toxicity of a bone-targeted ph-sensitive liposomal formulation in a bone metastasis tumor model in mice
AU - dos Santos Ferreira, Diego
AU - Jesus de Oliveira Pinto, Bruno Luís
AU - Kumar, Vidhya
AU - Cardoso, Valbert Nascimento
AU - Fernandes, Simone Odília
AU - Souza, Cristina Maria
AU - Cassali, Geovanni Dantas
AU - Moore, Anna
AU - Sosnovik, David E.
AU - Farrar, Christian T.
AU - Leite, Elaine Amaral
AU - Alves, Ricardo José
AU - de Oliveira, Mônica Cristina
AU - Guimarães, Alexander Ramos
AU - Caravan, Peter
N1 - Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/7
Y1 - 2017/7
N2 - 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.
AB - 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.
KW - Bisphosphonates
KW - Bone tumor
KW - Cardiotoxicity
KW - Doxorubicin
KW - Hydroxyapatite-targeting
UR - http://www.scopus.com/inward/record.url?scp=85019772353&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85019772353&partnerID=8YFLogxK
U2 - 10.1016/j.nano.2017.03.005
DO - 10.1016/j.nano.2017.03.005
M3 - Article
C2 - 28343016
AN - SCOPUS:85019772353
SN - 1549-9634
VL - 13
SP - 1693
EP - 1701
JO - Nanomedicine: Nanotechnology, Biology, and Medicine
JF - Nanomedicine: Nanotechnology, Biology, and Medicine
IS - 5
ER -