Systemic delivery of axitinib with nanohybrid liposomal nanoparticles inhibits hypoxic tumor growth

Title
Systemic delivery of axitinib with nanohybrid liposomal nanoparticles inhibits hypoxic tumor growth
Author(s)
김종오티르거네쉬라마사미최주연트란탄힙구세광[구세광]신범수[신범수]최한곤[최한곤]용철순
Keywords
STERICALLY STABILIZED LIPOSOMES; CHITOSAN NANOPARTICLES; POLYETHYLENE-GLYCOL; COMPLEX MICELLES; DRUG-DELIVERY; CANCER; HIF-1; DOXORUBICIN; THERAPY; TARGET
Issue Date
201501
Publisher
ROYAL SOC CHEMISTRY
Citation
JOURNAL OF MATERIALS CHEMISTRY B, v.3, no.3, pp.408 - 416
Abstract
Axitinib (AXT) is a potent and selective orally administered inhibitor of the vascular endothelial growth factor receptors 1-3 that contribute to the pathogenesis of solid tumors. The goal of the present study was to enhance the antiangiogenic and antitumor effects of AXT under hypoxia. Here we developed spherical polypeptide-coated hybrid liposomal nanoparticles (P-LNP/AXT) with a narrow size distribution and high loading efficiency. The cytotoxic effects of P-LNP/AXT on cancer cells were lower than those of AXT, and the human cancer cell lines SCC7, BT-474, and SH-SY5YP efficiently incorporated P-LNP/AXT. However, these formulations were not significantly internalized by the mouse macrophage cell line RAW 264.7, suggesting that they could evade the reticuloendothelial system. Western blotting analysis showed a significant increase in the level of expression of hydroxy-HIF-1 alpha when cells were treated with P-LNP/ AXT. The growth of tumors in mice treated with P-LNP/AXT was significantly inhibited compared with controls. Further, elevated levels of caspase-3 and poly (ADP-ribose) polymerase and reduced levels of platelet/endothelial cell adhesion molecule 1 (PECAM1, CD31) and Ki-67 in tumor cells suggested that tumor cells underwent apoptosis and that angiogenesis was inhibited within the tumor. Thus, P-LNP/AXT shows promise for cancer chemotherapy by inhibiting tumor angiogenesis.
URI
http://hdl.handle.net/YU.REPOSITORY/33720http://dx.doi.org/10.1039/c4tb01442a
ISSN
2050-750X
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약학대학 > 약학부 > Articles
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