Short interfering RNA delivered by a hybrid nanoparticle targeting VEGF: Biodistribution and anti-tumor effect.
Breast cancer treatment
Gene silence
Hybrid nanoparticles
RNA interference
Tumor reduction
Journal
Biochimica et biophysica acta. General subjects
ISSN: 1872-8006
Titre abrégé: Biochim Biophys Acta Gen Subj
Pays: Netherlands
ID NLM: 101731726
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
received:
25
03
2021
revised:
19
05
2021
accepted:
25
05
2021
pubmed:
2
6
2021
medline:
17
11
2021
entrez:
1
6
2021
Statut:
ppublish
Résumé
The use of RNA interference (iRNA) therapy has proved to be an interesting target therapy for the cancer treatment; however, siRNAs are unstable and quickly eliminated from the bloodstream. To face these barriers, the use of biocompatible and efficient nanocarriers emerges as an alternative to improve the success application of iRNA to the cancer, including breast cancer. A hybrid nanocarrier composed of calcium phosphate as the inorganic phase and a block copolymer containing polyanions as organic phase, named HNPs, was developed to deliver VEGF siRNA into metastatic breast cancer in mice. The particles presented a rounded shape by TEM images with average size measured by DLS suitable and biocompatible for biomedical applications. The XPS and EDS spectra confirmed the hybrid composition of the nanoparticles. Moreover, after intravenous administration, the particles accumulated mainly in the tumor site and kidneys, which demonstrates the tumor targeting accumulation through the Enhanced Permeability and Retention Effect (EPR). A significant decrease in size of the tumors treated with the nanoparticles containing siVEGF (HNPs-siVEGF) was observed and the reduction was related to enhanced tumor accumulation of siRNA as well as in vivo VEGF silencing at gene and protein levels. The hybrid system prepared was successful in promoting the RNAi effect in vivo with very low toxicity. This study shows the valuable development of a hybrid nanoparticle carrying VEGF siRNA, as well as their tumor targeting, accumulation and reduction in mice triple-negative breast cancer.
Sections du résumé
BACKGROUND
The use of RNA interference (iRNA) therapy has proved to be an interesting target therapy for the cancer treatment; however, siRNAs are unstable and quickly eliminated from the bloodstream. To face these barriers, the use of biocompatible and efficient nanocarriers emerges as an alternative to improve the success application of iRNA to the cancer, including breast cancer.
RESULTS
A hybrid nanocarrier composed of calcium phosphate as the inorganic phase and a block copolymer containing polyanions as organic phase, named HNPs, was developed to deliver VEGF siRNA into metastatic breast cancer in mice. The particles presented a rounded shape by TEM images with average size measured by DLS suitable and biocompatible for biomedical applications. The XPS and EDS spectra confirmed the hybrid composition of the nanoparticles. Moreover, after intravenous administration, the particles accumulated mainly in the tumor site and kidneys, which demonstrates the tumor targeting accumulation through the Enhanced Permeability and Retention Effect (EPR). A significant decrease in size of the tumors treated with the nanoparticles containing siVEGF (HNPs-siVEGF) was observed and the reduction was related to enhanced tumor accumulation of siRNA as well as in vivo VEGF silencing at gene and protein levels.
CONCLUSION
The hybrid system prepared was successful in promoting the RNAi effect in vivo with very low toxicity.
GENERAL SIGNIFICANCE
This study shows the valuable development of a hybrid nanoparticle carrying VEGF siRNA, as well as their tumor targeting, accumulation and reduction in mice triple-negative breast cancer.
Identifiants
pubmed: 34062235
pii: S0304-4165(21)00096-9
doi: 10.1016/j.bbagen.2021.129938
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
RNA, Small Interfering
0
Vascular Endothelial Growth Factor A
0
vascular endothelial growth factor A, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
129938Informations de copyright
Copyright © 2021. Published by Elsevier B.V.