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Targeted therapy of triple negative MDA-MB-468 breast cancer with curcumin delivered by epidermal growth factor-conjugated phospholipid nanoparticles

Triple-negative breast cancer (TNBC) is associated with poor survival as chemotherapy is currently limited to conventional cytotoxic agents. Curcumin has promising anticancer actions against TNBC, but its application is hindered by poor bioavailability and rapid degradation in vivo. In the present s...

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Autores principales: Jung, Kyung-Ho, Lee, Jin Hee, Park, Jin Won, Kim, Da Hae, Moon, Seung-Hwan, Cho, Young Seok, Lee, Kyung-Han
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5958779/
https://www.ncbi.nlm.nih.gov/pubmed/29805641
http://dx.doi.org/10.3892/ol.2018.8471
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author Jung, Kyung-Ho
Lee, Jin Hee
Park, Jin Won
Kim, Da Hae
Moon, Seung-Hwan
Cho, Young Seok
Lee, Kyung-Han
author_facet Jung, Kyung-Ho
Lee, Jin Hee
Park, Jin Won
Kim, Da Hae
Moon, Seung-Hwan
Cho, Young Seok
Lee, Kyung-Han
author_sort Jung, Kyung-Ho
collection PubMed
description Triple-negative breast cancer (TNBC) is associated with poor survival as chemotherapy is currently limited to conventional cytotoxic agents. Curcumin has promising anticancer actions against TNBC, but its application is hindered by poor bioavailability and rapid degradation in vivo. In the present study, curcumin-loaded phospholipid nanoparticles (Cur-NPs) conjugated with epidermal growth factor (EGF) were prepared for specific targeting of EGF receptors overexpressed in TNBC. NP formulation was performed by reacting EGF peptide with N-hydroxysuccinimide-Polyethylene Glycol-1,2-Distearoyl-sn-Glycero-3-Phosphoethanolamine (NHS-PEG(10000)-DSPE), followed by efficient curcumin loading through lipid film hydration. EGF conjugation did not significantly affect NP size, zeta potential or morphology. Specific targeting was confirmed by EGF receptor activation and blocking of (125)I-labeled NP binding by excess EGF. EGF-Cur-NP dose-dependently suppressed MDA-MB-468 TNBC cell survival (IC50, 620 nM), and completely abolished their capacity to form colonies. The cytotoxic effects were more potent compared with those of free curcumin or Cur-NP. In mice bearing MDA-MB-468 tumors, injections of 10 mg/kg EGF-Cur-NP caused a 59.1% retardation of tumor growth at 3 weeks compared with empty NP, whereas the antitumor effect of Cur-NP was weak. These results indicate that EGF-conjugated NHS-PEG(10000)-DSPE phospholipid NPs loaded with curcumin may be useful for treating TNBCs that overexpress the EGF receptor.
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spelling pubmed-59587792018-05-27 Targeted therapy of triple negative MDA-MB-468 breast cancer with curcumin delivered by epidermal growth factor-conjugated phospholipid nanoparticles Jung, Kyung-Ho Lee, Jin Hee Park, Jin Won Kim, Da Hae Moon, Seung-Hwan Cho, Young Seok Lee, Kyung-Han Oncol Lett Articles Triple-negative breast cancer (TNBC) is associated with poor survival as chemotherapy is currently limited to conventional cytotoxic agents. Curcumin has promising anticancer actions against TNBC, but its application is hindered by poor bioavailability and rapid degradation in vivo. In the present study, curcumin-loaded phospholipid nanoparticles (Cur-NPs) conjugated with epidermal growth factor (EGF) were prepared for specific targeting of EGF receptors overexpressed in TNBC. NP formulation was performed by reacting EGF peptide with N-hydroxysuccinimide-Polyethylene Glycol-1,2-Distearoyl-sn-Glycero-3-Phosphoethanolamine (NHS-PEG(10000)-DSPE), followed by efficient curcumin loading through lipid film hydration. EGF conjugation did not significantly affect NP size, zeta potential or morphology. Specific targeting was confirmed by EGF receptor activation and blocking of (125)I-labeled NP binding by excess EGF. EGF-Cur-NP dose-dependently suppressed MDA-MB-468 TNBC cell survival (IC50, 620 nM), and completely abolished their capacity to form colonies. The cytotoxic effects were more potent compared with those of free curcumin or Cur-NP. In mice bearing MDA-MB-468 tumors, injections of 10 mg/kg EGF-Cur-NP caused a 59.1% retardation of tumor growth at 3 weeks compared with empty NP, whereas the antitumor effect of Cur-NP was weak. These results indicate that EGF-conjugated NHS-PEG(10000)-DSPE phospholipid NPs loaded with curcumin may be useful for treating TNBCs that overexpress the EGF receptor. D.A. Spandidos 2018-06 2018-04-12 /pmc/articles/PMC5958779/ /pubmed/29805641 http://dx.doi.org/10.3892/ol.2018.8471 Text en Copyright: © Jung et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Jung, Kyung-Ho
Lee, Jin Hee
Park, Jin Won
Kim, Da Hae
Moon, Seung-Hwan
Cho, Young Seok
Lee, Kyung-Han
Targeted therapy of triple negative MDA-MB-468 breast cancer with curcumin delivered by epidermal growth factor-conjugated phospholipid nanoparticles
title Targeted therapy of triple negative MDA-MB-468 breast cancer with curcumin delivered by epidermal growth factor-conjugated phospholipid nanoparticles
title_full Targeted therapy of triple negative MDA-MB-468 breast cancer with curcumin delivered by epidermal growth factor-conjugated phospholipid nanoparticles
title_fullStr Targeted therapy of triple negative MDA-MB-468 breast cancer with curcumin delivered by epidermal growth factor-conjugated phospholipid nanoparticles
title_full_unstemmed Targeted therapy of triple negative MDA-MB-468 breast cancer with curcumin delivered by epidermal growth factor-conjugated phospholipid nanoparticles
title_short Targeted therapy of triple negative MDA-MB-468 breast cancer with curcumin delivered by epidermal growth factor-conjugated phospholipid nanoparticles
title_sort targeted therapy of triple negative mda-mb-468 breast cancer with curcumin delivered by epidermal growth factor-conjugated phospholipid nanoparticles
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5958779/
https://www.ncbi.nlm.nih.gov/pubmed/29805641
http://dx.doi.org/10.3892/ol.2018.8471
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