PUBLICATION
Nanoparticle-mediated targeting of phosphatidylinositol-3-kinase signaling inhibits angiogenesis
- Authors
- Harfouche, R., Basu, S., Soni, S., Hentschel, D.M., Mashelkar, R.A., and Sengupta, S.
- ID
- ZDB-PUB-090819-11
- Date
- 2009
- Source
- Angiogenesis 12(4): 325-338 (Journal)
- Registered Authors
- Hentschel, Dirk
- Keywords
- Angiogenesis, Nanoparticles, PI3 kinase
- MeSH Terms
-
- Adenocarcinoma/blood supply*
- Animals
- Breast Neoplasms/blood supply*
- Carcinoma, Lewis Lung/blood supply*
- Cell Line, Tumor/transplantation
- Cells, Cultured/drug effects
- Chromones/administration & dosage*
- Chromones/pharmacology
- Chromones/therapeutic use
- Drug Carriers/administration & dosage*
- Endothelial Cells/cytology
- Endothelial Cells/drug effects*
- Humans
- Melanoma, Experimental/blood supply*
- Mice
- Morpholines/administration & dosage*
- Morpholines/pharmacology
- Morpholines/therapeutic use
- Nanocapsules/administration & dosage*
- Nanocapsules/ultrastructure
- Neoplasm Proteins/antagonists & inhibitors*
- Neovascularization, Pathologic/drug therapy*
- Neovascularization, Physiologic/drug effects*
- Phosphatidylinositol 3-Kinases/antagonists & inhibitors*
- Phosphorylation/drug effects
- Protein Processing, Post-Translational/drug effects*
- Proto-Oncogene Proteins c-akt/antagonists & inhibitors*
- Umbilical Veins
- Xenograft Model Antitumor Assays
- Zebrafish
- PubMed
- 19685150 Full text @ Angiogenesis
Citation
Harfouche, R., Basu, S., Soni, S., Hentschel, D.M., Mashelkar, R.A., and Sengupta, S. (2009) Nanoparticle-mediated targeting of phosphatidylinositol-3-kinase signaling inhibits angiogenesis. Angiogenesis. 12(4):325-338.
Abstract
OBJECTIVE: Dysregulation of the phosphatidylinositol-3-kinase (PI3K) signaling pathway is a hallmark of human cancer, occurring in a majority of tumors. Activation of this pathway is critical for transformation and also for the angiogenic switch, which is a key step for tumor progression. The objective of this study was to engineer a PI3K inhibitor-loaded biodegradable nanoparticle and to evaluate its efficacy. METHODS AND RESULTS: Here we report that a nanoparticle-enabled targeting of the PI3K pathway results in inhibition of downstream Akt phosphorylation, leading to inhibition of proliferation and induction of apoptosis of B16/F10 melanoma. It, however, failed to exert a similar activity on MDA-MB-231 breast cancer cells, resulting from reduced internalization and processing of nanoparticles in this cell line. Excitingly, the nanoparticle-enabled targeting of the PI3K pathway resulted in inhibition of endothelial cell proliferation and tubulogenesis, two key steps in tumor angiogenesis. Furthermore, it inhibited both B16/F10- and MDA-MB-231-induced angiogenesis in a zebrafish tumor xenotransplant model. CONCLUSION: Our study, for the first time, shows that targeting of the PI3K pathway using nanoparticles can offer an attractive strategy for inhibiting tumor angiogenesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping