PUBLICATION
Combined tumor- and neovascular-"dual targeting" gene/chemo-therapy suppresses tumor growth and angiogenesis
- Authors
- Xu, B., Jin, Q., Zeng, J., Yu, T., Chen, Y., Li, S., Gong, D., He, L., Tan, X., Yang, L., He, G., Wu, J., Song, X.R.
- ID
- ZDB-PUB-160913-13
- Date
- 2016
- Source
- ACS applied materials & interfaces 8(39): 25753-25769 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Antineoplastic Agents
- Cell Line, Tumor
- Humans
- Mice
- Nanoparticles
- Neoplasms*
- Neovascularization, Pathologic
- Paclitaxel
- PubMed
- 27615739 Full text @ ACS Appl. Mater. Interfaces
Citation
Xu, B., Jin, Q., Zeng, J., Yu, T., Chen, Y., Li, S., Gong, D., He, L., Tan, X., Yang, L., He, G., Wu, J., Song, X.R. (2016) Combined tumor- and neovascular-"dual targeting" gene/chemo-therapy suppresses tumor growth and angiogenesis. ACS applied materials & interfaces. 8(39):25753-25769.
Abstract
A rational combination is critical to achieve efficiently synergistic therapeutic efficacy for tumor treatment. Hence, we designed novel anti-tumor combinations (T-NPs) by integrating the tumor vascular and tumor cells dual-targeting ligand with anti-angiogenesis/anti-tumor agents. The truncated bFGF peptide (tbFGF), which could effectively bind to FGFR1 overexpressed on tumor neovasculature endothelial cells and tumor cells, was selected to modify PLGA nanoparticles (D/P-NPs) simultaneously loaded with PEDF gene and paclitaxel in this study. The obtained T-NPs with better pharmaceutical properties had elevated cytotoxicity and enhanced expression of PEDF and α-tubulin on FGFR1-overexpressing cells. The uptake of T-NPs increased in C26 cells, probably mediated by tbFGF via specific recognization of the overexpressed FGFR1. T-NPs dramatically disrupted the tube formation of primary human umbilical vein endothelial cells (HUVECs), and displayed improved anti-angiogenic activity in transgenic zebrafish model and alginate-encapsulated tumor cell model. More importantly, T-NPs achieved a markedly higher antitumor efficacy in C26 tumor-bearing mice model. The anti-tumor effect involved the inhibition of tumor cell proliferation and angiogenesis, induction of apoptosis and down-regulation of FGFR1. The enhanced anti-tumor activity of T-NPs probably resulted from the raised distribution in tumor tissues. In addition, T-NPs had no obvious toxicity through the weight monitoring, serological and biochemical analysis, as well as H&E staining. These results revealed that T-NPs, an active targeting gene/chemo-therapy, indeed had superior antitumor efficacy and negligible side effect, suggesting that this novel combination was potential for tumor therapy as a new treatment strategy and the tbFGF modified nanoparticles could be applied to a wide range of tumor-genetic therapies and/or tumor-chemical therapies.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping