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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
최한곤
Keywords
STERICALLY STABILIZED LIPOSOMES; CHITOSAN NANOPARTICLES; POLYETHYLENE-GLYCOL; COMPLEX MICELLES; DRUG-DELIVERY; CANCER; HIF-1; DOXORUBICIN; THERAPY; TARGET
Issue Date
2015-01
Publisher
ROYAL SOC CHEMISTRY
Citation
JOURNAL OF MATERIALS CHEMISTRY B, v. 3, No. 3, Page. 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://pubs.rsc.org/-/content/articlehtml/2015/tb/c4tb01442ahttps://repository.hanyang.ac.kr/handle/20.500.11754/100622
ISSN
2050-750X; 2050-7518
DOI
10.1039/c4tb01442a
Appears in Collections:
COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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