Sustained inhibition of cMET-VEGFR2 signaling using liposome-mediated delivery increases efficacy and reduces toxicity in kidney cancer
作者: Ashish A. KulkarniVijay Elakkya VijaykumarSiva Kumar NatarajanShiladitya SenguptaVenkata S. Sabbisetti
作者单位: 1Division of Biomedical Engineering, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
2Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
3Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
4Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, USA
5Dana Farber Cancer Institute, Boston, MA, USA
刊名: Nanomedicine: Nanotechnology, Biology, and Medicine, 2016, Vol.12 (7), pp.1853-1861
来源数据库: Elsevier Journal
DOI: 10.1016/j.nano.2016.04.002
关键词: Renal cell carcinomaLiposomesc-Met inhibitorKinase inhibitor delivery
原始语种摘要: Abstract(#br)c-Met pathway is implicated in the resistance to anti-VEGF therapy in renal cell carcinoma (RCC). However, clinical translation of therapies targeting these pathways has been limited due to dose-limiting toxicities, feedback signaling, and low intratumoral drug accumulation. Here, we developed liposomes encapsulating a multi-receptor tyrosine kinase inhibitor (XL184) to explore the possibility of improving intratumoral concentration, enhancing antitumor efficacy and reducing toxicities. The liposomes showed increased cytotoxicity than XL184, and resulted in a sustained inhibition of phosphorylation of Met, AKT and MAPK pathways in RCC cells. In a RCC tumor xenograft model, the liposomes induced sustained inhibition of tumor growth as compared to XL184, consistent with higher...
全文获取路径: Elsevier  (合作)
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