期刊
PHARMACEUTICAL RESEARCH
卷 31, 期 9, 页码 2490-2502出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-014-1345-z
关键词
C-6-ceramide; EGFR; gadolinium; MRI; nanoemulsion; ovarian cancer; platinum
资金
- NIH [R43 CA144591, U54 CA151881]
- Massachusetts Life Science Center Internship Challenge
Platinum-based chemotherapy is the treatment of choice for malignant epithelial ovarian cancers, but generalized toxicity and platinum resistance limits its use. Theranostic nanoemulsion with a novel platinum prodrug, myrisplatin, and the pro-apoptotic agent, C-6-ceramide, were designed to overcome these limitations. The nanoemulsions, including ones with an EGFR binding peptide and gadolinium, were made using generally regarded as safe grade excipients and a high shear microfluidization process. Efficacy was evaluated in ovarian cancer cells, SKOV3, A2780 and A2780(CP). The nanoemulsion with particle size < 150 nm were stable in plasma and parenteral fluids for 24 h. Ovarian cancer cells in vitro efficiently took up the non-targeted and EGFR-targeted nanoemulsions; improved cytotoxicity was observed for the these nanoemulsions with the latter showing a 50-fold drop in the IC50 in SKOV3 cells as compared to cisplatin alone. The addition of gadolinium did not affect cell viability in vitro, but showed relaxation times comparable to Magnevist(A (R)). The myrisplatin/C-6-ceramide nanoemulsion synergistically enhanced in vitro cytotoxicity. An EGFR binding peptide addition further increased in vitro cytotoxicity in EGFR positive cancer cells. The diagnostic version showed MR imaging similar to the clinically relevant MagnevistA (R) and may be suitable as a theranostic for ovarian cancer.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据