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Pre-Clinical Evaluation of rHDL Encapsulated Retinoids for the Treatment of Neuroblastoma
Despite major advances in pediatric cancer research, there has been only modest progress in the survival of children with high risk neuroblastoma (NB) (HRNB). The long term survival rates of HRNB in the United States are still only 30–50%. Due to resistance that often develops during therapy, develo...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3891009/ https://www.ncbi.nlm.nih.gov/pubmed/24459664 http://dx.doi.org/10.3389/fped.2013.00006 |
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author | Sabnis, Nirupama Pratap, Suraj Akopova, Irina Bowman, Paul W. Lacko, Andras G. |
author_facet | Sabnis, Nirupama Pratap, Suraj Akopova, Irina Bowman, Paul W. Lacko, Andras G. |
author_sort | Sabnis, Nirupama |
collection | PubMed |
description | Despite major advances in pediatric cancer research, there has been only modest progress in the survival of children with high risk neuroblastoma (NB) (HRNB). The long term survival rates of HRNB in the United States are still only 30–50%. Due to resistance that often develops during therapy, development of new effective strategies is essential to improve the survival and overcome the tendency of HRNB patients to relapse subsequent to initial treatment. Current chemotherapy regimens also have a serious limitation due to off target toxicity. In the present work, we evaluated the potential application of reconstituted high density lipoprotein (rHDL) containing fenretinide (FR) nanoparticles as a novel approach to current NB therapeutics. The characterization and stability studies of rHDL-FR nanoparticles showed small size (<40 nm) and high encapsulation efficiency. The cytotoxicity studies of free FR vs. rHDL/FR toward the NB cell lines SK-N-SH and SMS-KCNR showed 2.8- and 2-fold lower IC(50) values for the rHDL encapsulated FR vs. free FR. More importantly, the IC(50) value for retinal pigment epithelial cells (ARPE-19), a recipient of off target toxicity during FR therapy, was over 40 times higher for the rHDL/FR as compared to that of free FR. The overall improvement in in vitro selective therapeutic efficiency was thus about 100-fold upon encapsulation of the drug into the rHDL nanoparticles. These studies support the potential value of this novel drug delivery platform for treating pediatric cancers in general, and NB in particular. |
format | Online Article Text |
id | pubmed-3891009 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-38910092014-01-23 Pre-Clinical Evaluation of rHDL Encapsulated Retinoids for the Treatment of Neuroblastoma Sabnis, Nirupama Pratap, Suraj Akopova, Irina Bowman, Paul W. Lacko, Andras G. Front Pediatr Pediatrics Despite major advances in pediatric cancer research, there has been only modest progress in the survival of children with high risk neuroblastoma (NB) (HRNB). The long term survival rates of HRNB in the United States are still only 30–50%. Due to resistance that often develops during therapy, development of new effective strategies is essential to improve the survival and overcome the tendency of HRNB patients to relapse subsequent to initial treatment. Current chemotherapy regimens also have a serious limitation due to off target toxicity. In the present work, we evaluated the potential application of reconstituted high density lipoprotein (rHDL) containing fenretinide (FR) nanoparticles as a novel approach to current NB therapeutics. The characterization and stability studies of rHDL-FR nanoparticles showed small size (<40 nm) and high encapsulation efficiency. The cytotoxicity studies of free FR vs. rHDL/FR toward the NB cell lines SK-N-SH and SMS-KCNR showed 2.8- and 2-fold lower IC(50) values for the rHDL encapsulated FR vs. free FR. More importantly, the IC(50) value for retinal pigment epithelial cells (ARPE-19), a recipient of off target toxicity during FR therapy, was over 40 times higher for the rHDL/FR as compared to that of free FR. The overall improvement in in vitro selective therapeutic efficiency was thus about 100-fold upon encapsulation of the drug into the rHDL nanoparticles. These studies support the potential value of this novel drug delivery platform for treating pediatric cancers in general, and NB in particular. Frontiers Media S.A. 2013-03-21 /pmc/articles/PMC3891009/ /pubmed/24459664 http://dx.doi.org/10.3389/fped.2013.00006 Text en Copyright © 2013 Sabnis, Pratap, Akopova, Bowman and Lacko. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc. |
spellingShingle | Pediatrics Sabnis, Nirupama Pratap, Suraj Akopova, Irina Bowman, Paul W. Lacko, Andras G. Pre-Clinical Evaluation of rHDL Encapsulated Retinoids for the Treatment of Neuroblastoma |
title | Pre-Clinical Evaluation of rHDL Encapsulated Retinoids for the Treatment of Neuroblastoma |
title_full | Pre-Clinical Evaluation of rHDL Encapsulated Retinoids for the Treatment of Neuroblastoma |
title_fullStr | Pre-Clinical Evaluation of rHDL Encapsulated Retinoids for the Treatment of Neuroblastoma |
title_full_unstemmed | Pre-Clinical Evaluation of rHDL Encapsulated Retinoids for the Treatment of Neuroblastoma |
title_short | Pre-Clinical Evaluation of rHDL Encapsulated Retinoids for the Treatment of Neuroblastoma |
title_sort | pre-clinical evaluation of rhdl encapsulated retinoids for the treatment of neuroblastoma |
topic | Pediatrics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3891009/ https://www.ncbi.nlm.nih.gov/pubmed/24459664 http://dx.doi.org/10.3389/fped.2013.00006 |
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