期刊论文详细信息
JOURNAL OF CONTROLLED RELEASE 卷:180
A diaCEST MRI approach for monitoring liposomal accumulation in tumors
Article
Chan, Kannie W. Y.1,2,3,8  Yu, Tao3,4  Qiao, Yuan6,7  Liu, Qiang6,7  Yang, Ming3,4  Patel, Himatkumar3  Liu, Guanshu1,2  Kinzler, Kenneth W.6,7  Vogelstein, Bert6,7  Bulte, Jeff W. M.1,2,4,8  van Zijl, Peter C. M.1,2  Hanes, Justin3,4,5  Zhou, Shibin6,7  McMahon, Michael T.1,2,3 
[1] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Div MR Res, Baltimore, MD 21287 USA
[2] Kennedy Krieger Inst, FM Kirby Res Ctr Funct Brain Imaging, Baltimore, MD 21205 USA
[3] Johns Hopkins Univ, Sch Med, Ctr Nanomed, Baltimore, MD 21287 USA
[4] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA
[5] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Dept Ophthalmol, Baltimore, MD 21287 USA
[6] Hopkins Kimmel Comprehens Canc Ctr, Ludwig Ctr, Baltimore, MD 21287 USA
[7] Hopkins Kimmel Comprehens Canc Ctr, Howard Hughes Med Inst, Baltimore, MD 21287 USA
[8] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Cellular Imaging Sect & Vasc Biol Program, Baltimore, MD 21205 USA
关键词: CEST;    MRI;    Liposomes;    Barbituric acid;    Doxorubicin;    Tumor necrosis factor;   
DOI  :  10.1016/j.jconrel.2014.02.005
来源: Elsevier
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【 摘 要 】

Nanocarrier-based chemotherapy allows preferential delivery of therapeutics to tumors and has been found to improve the efficacy of cancer treatment. However, difficulties in tracking nanocarriers and evaluating their pharmacological fates in patients have limited judicious selection of patients to those who might most benefit from nanotherapeutics. To enable the monitoring of nanocarriers in vivo, we developed MRI-traceable diamagnetic Chemical Exchange Saturation Transfer (diaCEST) liposomes. The diaCEST liposomes were based on the clinical formulation of liposomal doxorubicin (i.e. DOXIL (R)) and were loaded with barbituric acid (BA), a small, organic, biocompatible diaCEST contrast agent. The optimized diaCEST liposomal formulation with a BA-to-lipid ratio of 25% exhibited 30% contrast enhancement at B-1 = 4.7 mu T in vitro. The contrast was stable, with similar to 80% of the initial CEST signal sustained over 8 h in vitro. We used the diaCEST liposomes to monitor the response to tumor necrosis factor-alpha (TNF-alpha), an agent in clinical trials that increases vascular permeability and uptake of nanocarriers into tumors. After systemic administration of diaCEST liposomes to mice bearing CT26 tumors, we found an average diaCEST contrast at the BA frequency (5 ppm) of 0.4% at B1 = 4.7 mu T while if TNF-alpha was co-administered the contrast increased to 1.5%. This novel approach provides a non-radioactive, non-metallic, biocompatible, semi-quantitative, and clinically translatable approach to evaluate the tumor targeting of stealth liposomes in vivo, which may enable personalized nanomedicine. (C) 2014 Elsevier B. V. All rights reserved.

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