Cargando…
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...
Autores principales: | , , , , , , |
---|---|
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 |
_version_ | 1784582161613979648 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8508707 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT linxiaomin constructionofil13receptora2targetingresveratrolnanoparticlesagainstglioblastomacellstherapeuticefficacyandmoleculareffects AT shixiaoxiao constructionofil13receptora2targetingresveratrolnanoparticlesagainstglioblastomacellstherapeuticefficacyandmoleculareffects AT xiongle constructionofil13receptora2targetingresveratrolnanoparticlesagainstglioblastomacellstherapeuticefficacyandmoleculareffects AT niejunhua constructionofil13receptora2targetingresveratrolnanoparticlesagainstglioblastomacellstherapeuticefficacyandmoleculareffects AT yehaishan constructionofil13receptora2targetingresveratrolnanoparticlesagainstglioblastomacellstherapeuticefficacyandmoleculareffects AT dujinzi constructionofil13receptora2targetingresveratrolnanoparticlesagainstglioblastomacellstherapeuticefficacyandmoleculareffects AT liujia constructionofil13receptora2targetingresveratrolnanoparticlesagainstglioblastomacellstherapeuticefficacyandmoleculareffects |