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Angiogenesis. 2009;12(4):325-38. doi: 10.1007/s10456-009-9154-4.

Nanoparticle-mediated targeting of phosphatidylinositol-3-kinase signaling inhibits angiogenesis.

Author information

1
Harvard-MIT Division of Health Sciences and Technology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

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.

PMID:
19685150
DOI:
10.1007/s10456-009-9154-4
[Indexed for MEDLINE]

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