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Construction of IL-13 Receptor α2-Targeting Resveratrol Nanoparticles against Glioblastoma Cells: Therapeutic Efficacy and Molecular Effects

Glioblastoma multiforme (GBM) is the most common lethal primary brain malignancy without reliable therapeutic drugs. IL-13Rα2 is frequently expressed in GBMs as a molecular marker. Resveratrol (Res) effectively inhibits GBM cell growth but has not been applied in vivo because of its low brain bioava...

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Autores principales: Lin, Xiao-Min, Shi, Xiao-Xiao, Xiong, Le, Nie, Jun-Hua, Ye, Hai-Shan, Du, Jin-Zi, Liu, Jia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508707/
https://www.ncbi.nlm.nih.gov/pubmed/34638961
http://dx.doi.org/10.3390/ijms221910622
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author Lin, Xiao-Min
Shi, Xiao-Xiao
Xiong, Le
Nie, Jun-Hua
Ye, Hai-Shan
Du, Jin-Zi
Liu, Jia
author_facet Lin, Xiao-Min
Shi, Xiao-Xiao
Xiong, Le
Nie, Jun-Hua
Ye, Hai-Shan
Du, Jin-Zi
Liu, Jia
author_sort Lin, Xiao-Min
collection PubMed
description Glioblastoma multiforme (GBM) is the most common lethal primary brain malignancy without reliable therapeutic drugs. IL-13Rα2 is frequently expressed in GBMs as a molecular marker. Resveratrol (Res) effectively inhibits GBM cell growth but has not been applied in vivo because of its low brain bioavailability when administered systemically. A sustained-release and GBM-targeting resveratrol form may overcome this therapeutic dilemma. To achieve this goal, encapsulated Res 30 ± 4.8 nm IL-13Rα2-targeting nanoparticles (Pep-PP@Res) were constructed. Ultraviolet spectrophotometry revealed prolonged Res release (about 25%) from Pep-PP@Res in 48 h and fluorescent confocal microscopy showed the prolonged intracellular Res retention time of Pep-PP@Res (>24 h) in comparison with that of free Res (<4 h) and PP@Res (<4 h). MTT and EdU cell proliferation assays showed stronger suppressive effects of Pep-PP@Res on rat C6 GBM cells than that of PP@Res (p = 0.024) and Res (p = 0.009) when used twice for 4 h/day. Pep-PP@Res had little toxic effect on normal rat brain cells. The in vivo anti-glioblastoma effects of Res can be distinctly improved in the form of Pep-PP@Res nanoparticles via activating JNK signaling, upregulating proapoptosis gene expression and, finally, resulting in extensive apoptosis. Pep-PP@Res with sustained release and GBM-targeting properties would be suitable for in vivo management of GBMs.
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spelling pubmed-85087072021-10-13 Construction of IL-13 Receptor α2-Targeting Resveratrol Nanoparticles against Glioblastoma Cells: Therapeutic Efficacy and Molecular Effects Lin, Xiao-Min Shi, Xiao-Xiao Xiong, Le Nie, Jun-Hua Ye, Hai-Shan Du, Jin-Zi Liu, Jia Int J Mol Sci Article Glioblastoma multiforme (GBM) is the most common lethal primary brain malignancy without reliable therapeutic drugs. IL-13Rα2 is frequently expressed in GBMs as a molecular marker. Resveratrol (Res) effectively inhibits GBM cell growth but has not been applied in vivo because of its low brain bioavailability when administered systemically. A sustained-release and GBM-targeting resveratrol form may overcome this therapeutic dilemma. To achieve this goal, encapsulated Res 30 ± 4.8 nm IL-13Rα2-targeting nanoparticles (Pep-PP@Res) were constructed. Ultraviolet spectrophotometry revealed prolonged Res release (about 25%) from Pep-PP@Res in 48 h and fluorescent confocal microscopy showed the prolonged intracellular Res retention time of Pep-PP@Res (>24 h) in comparison with that of free Res (<4 h) and PP@Res (<4 h). MTT and EdU cell proliferation assays showed stronger suppressive effects of Pep-PP@Res on rat C6 GBM cells than that of PP@Res (p = 0.024) and Res (p = 0.009) when used twice for 4 h/day. Pep-PP@Res had little toxic effect on normal rat brain cells. The in vivo anti-glioblastoma effects of Res can be distinctly improved in the form of Pep-PP@Res nanoparticles via activating JNK signaling, upregulating proapoptosis gene expression and, finally, resulting in extensive apoptosis. Pep-PP@Res with sustained release and GBM-targeting properties would be suitable for in vivo management of GBMs. MDPI 2021-09-30 /pmc/articles/PMC8508707/ /pubmed/34638961 http://dx.doi.org/10.3390/ijms221910622 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lin, Xiao-Min
Shi, Xiao-Xiao
Xiong, Le
Nie, Jun-Hua
Ye, Hai-Shan
Du, Jin-Zi
Liu, Jia
Construction of IL-13 Receptor α2-Targeting Resveratrol Nanoparticles against Glioblastoma Cells: Therapeutic Efficacy and Molecular Effects
title Construction of IL-13 Receptor α2-Targeting Resveratrol Nanoparticles against Glioblastoma Cells: Therapeutic Efficacy and Molecular Effects
title_full Construction of IL-13 Receptor α2-Targeting Resveratrol Nanoparticles against Glioblastoma Cells: Therapeutic Efficacy and Molecular Effects
title_fullStr Construction of IL-13 Receptor α2-Targeting Resveratrol Nanoparticles against Glioblastoma Cells: Therapeutic Efficacy and Molecular Effects
title_full_unstemmed Construction of IL-13 Receptor α2-Targeting Resveratrol Nanoparticles against Glioblastoma Cells: Therapeutic Efficacy and Molecular Effects
title_short Construction of IL-13 Receptor α2-Targeting Resveratrol Nanoparticles against Glioblastoma Cells: Therapeutic Efficacy and Molecular Effects
title_sort construction of il-13 receptor α2-targeting resveratrol nanoparticles against glioblastoma cells: therapeutic efficacy and molecular effects
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508707/
https://www.ncbi.nlm.nih.gov/pubmed/34638961
http://dx.doi.org/10.3390/ijms221910622
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