Combined Tumor- and Neovascular-"Dual Targeting" Gene/Chemo-Therapy Suppresses Tumor Growth and Angiogenesis.
ACS Appl Mater Interfaces
; 8(39): 25753-25769, 2016 Oct 05.
Article
em En
| MEDLINE
| ID: mdl-27615739
ABSTRACT
A rational combination is critical to achieve efficiently synergistic therapeutic efficacy for tumor treatment. Hence, we designed novel antitumor combinations (T-NPs) by integrating the tumor vascular and tumor cells dual-targeting ligand with antiangiogenesis/antitumor 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 antiangiogenic activity in the transgenic zebrafish model and the alginate-encapsulated tumor cell model. More importantly, T-NPs achieved a markedly higher antitumor efficacy in the C26 tumor-bearing mice model. The antitumor effect involved the inhibition of tumor cell proliferation and angiogenesis, induction of apoptosis, and down-regulation of FGFR1. The enhanced antitumor activity of T-NPs probably resulted from the raised distribution in tumor tissues. In addition, T-NPs had no obvious toxicity as evaluated by weight monitoring, serological/biochemical analyses, and 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 is a potential tumor therapy and a new treatment strategy and that the tbFGF modified nanoparticles could be applied to a wide range of tumor-genetic therapies and/or tumor-chemical therapies.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
ACS Appl Mater Interfaces
Assunto da revista:
BIOTECNOLOGIA
/
ENGENHARIA BIOMEDICA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
China