A diaCEST MRI approach for monitoring liposomal accumulation in tumors

Kannie W Y Chan, Tao Yu, Yuan Qiao, Qiang Liu, Ming Yang, Himatkumar Patel, Guanshu Liu, Kenneth W Kinzler, Bert Vogelstein, Jeff W Bulte, Peter C Van Zijl, Justin S Hanes, Shibin Zhou, Michael T Mcmahon

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)51-59
Number of pages9
JournalJournal of Controlled Release
Volume180
Issue number1
DOIs
StatePublished - Apr 28 2014

Fingerprint

Liposomes
Neoplasms
Tumor Necrosis Factor-alpha
Nanomedicine
Capillary Permeability
Patient Selection
Contrast Media
Clinical Trials
Pharmacology
Lipids
Drug Therapy
barbituric acid
In Vitro Techniques
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Medicine(all)

Cite this

A diaCEST MRI approach for monitoring liposomal accumulation in tumors. / Chan, Kannie W Y; Yu, Tao; Qiao, Yuan; Liu, Qiang; Yang, Ming; Patel, Himatkumar; Liu, Guanshu; Kinzler, Kenneth W; Vogelstein, Bert; Bulte, Jeff W; Van Zijl, Peter C; Hanes, Justin S; Zhou, Shibin; Mcmahon, Michael T.

In: Journal of Controlled Release, Vol. 180, No. 1, 28.04.2014, p. 51-59.

Research output: Contribution to journalArticle

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