A diaCEST MRI approach for monitoring liposomal accumulation in tumors

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

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Author(s)

  • Tao Yu
  • Yuan Qiao
  • Qiang Liu
  • Ming Yang
  • Himatkumar Patel
  • Guanshu Liu
  • Kenneth W. Kinzler
  • Bert Vogelstein
  • Jeff W.M. Bulte
  • Peter C.M. Van Zijl
  • Justin Hanes
  • Shibin Zhou
  • Michael T. McMahon

Detail(s)

Original languageEnglish
Pages (from-to)51-59
Journal / PublicationJournal of Controlled Release
Volume180
Issue number1
Online published15 Feb 2014
Publication statusPublished - 28 Apr 2014
Externally publishedYes

Abstract

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®) 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 B1 = 4.7 μT in vitro. The contrast was stable, with ∼ 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-α), 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 μT while if TNF-α 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. © 2014 Elsevier B.V. All rights reserved.

Research Area(s)

  • Barbituric acid, CEST, Doxorubicin, Liposomes, MRI, Tumor necrosis factor

Citation Format(s)

A diaCEST MRI approach for monitoring liposomal accumulation in tumors. / Chan, Kannie W.Y.; Yu, Tao; Qiao, Yuan et al.
In: Journal of Controlled Release, Vol. 180, No. 1, 28.04.2014, p. 51-59.

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review