Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Ding, X; Su, Y; Wang, C; Zhang, F; Chen, K; Wang, Y; Li, M; Wang, W.
Synergistic Suppression of Tumor Angiogenesis by the Co-delivering of Vascular Endothelial Growth Factor Targeted siRNA and Candesartan Mediated by Functionalized Carbon Nanovectors.
ACS Appl Mater Interfaces. 2017; 9(28):23353-23369
Doi: 10.1021/acsami.7b04971
Web of Science
PubMed
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- Co-Autor*innen der Med Uni Graz
- Zhang Fangrong
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- Abstract:
- Single-walled carbon nanotubes (SWNTs) with unique physicochemical properties have exhibited promising biomedical applications as drug and gene carriers. In this study, polyethylenimine (PEI)-modified SWNT conjugates linked with candesartan (CD) were developed to deliver vascular endothelial growth factor (VEGF)-targeted siRNA (siVEGF) for the synergistic and targeted treatment of tumor angiogenesis. The characterization results revealed that SWNT-PEI-CD conjugates were successfully synthesized and exhibited desirable dispersibility and superior stability. Confocal laser scanning microscopy (CLSM) and flow cytometry (FCM) results showed that SWNT-PEI-CD/siVEGF complexes could achieve high cellular uptake and specific intracellular distribution of siRNA in AT1R overexpressed PANC-1 cells. Strong down-regulation of VEGF was also verified by qualitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blot in complex-treated PANC-1 cells. The in vitro angiogenesis assay showed that SWNT-PEI-CD/siVEGF complexes highly inhibited tube formation of human umbilical vein endothelial cells. Furthermore, in vivo observation in PANC-1 xenografted nude mice demonstrated that SWNT-PEI-CD/siVEGF complexes exhibited significant distribution at tumor sites and caused obvious inhibition of tumor growth and tumor-associated angiogenesis repression induced by the drug combination of CD and siVEGF. Finally, a WST-1 assay indicated that SWNT-PEI-CD possessed low cytotoxicity, and a hemolysis test showed good biocompatibility of SWNT-PEI-CD. Hematological and histological analyses confirmed that SWNT-PEI-CD/siVEGF complexes did not cause any obvious toxic effects to blood and major organs. These findings suggested that the SWNT-PEI-CD/siVEGF co-delivery system with tumor-targeting specificity, improved endosomal escaping properties, and collaboration of angiogenesis inhibition could be a prospective method for efficient tumor antiangiogenic therapy.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Benzimidazoles -
- Cell Line, Tumor -
- Humans -
- Mice -
- Mice, Nude -
- Nanotubes, Carbon -
- Neoplasms -
- Neovascularization, Pathologic -
- Polyethyleneimine -
- Prospective Studies -
- RNA, Small Interfering -
- Tetrazoles -
- Vascular Endothelial Growth Factor A -
- Find related publications in this database (Keywords)
- single-walled carbon nanotubes
- candesartan
- VEGF-targeted siRNA
- synergistic inhibition
- tumor angiogenesis