Label-free CEST MRI detection of citicoline-liposome drug delivery in ischemic stroke

Huanling Liu, Anna Jablonska, Yuguo Li, Suyi Cao, Dexiang Liu, Hanwei Chen, Peter C Van Zijl, Jeff W Bulte, Miroslaw Janowski, Piotr Walczak, Guanshu Liu

Research output: Contribution to journalArticle

Abstract

Citicoline (CDPC) is a natural supplement with well-documented neuroprotective effects in the treatment of neurodegenerative diseases. In the present study, we sought to exploit citicoline as a theranostic agent with its inherent chemical exchange saturation transfer (CEST) MRI signal, which can be directly used as an MRI guidance in the citicoline drug delivery. Our in vitro CEST MRI results showed citicoline has two inherent CEST signals at +1 and +2 ppm, attributed to exchangeable hydroxyl and amine protons, respectively. To facilitate the targeted drug delivery of citicoline to ischemic regions, we prepared liposomes encapsulating citicoline (CDPC-lipo) and characterized the particle properties and CEST MRI properties. The in vivo CEST MRI detection of liposomal citicoline was then examined in a rat brain model of unilateral transient ischemia induced by a two-hour middle cerebral artery occlusion. The results showed that the delivery of CPDC-lipo to the brain ischemic areas could be monitored and quantified by CEST MRI. When administered intra-arterially, CDPC-lipo clearly demonstrated a detectable CEST MRI contrast at 2 ppm. CEST MRI revealed that liposomes preferentially accumulated in the areas of ischemia with a disrupted blood-brain-barrier. We furthermore used CEST MRI to detect the improvement in drug delivery using CDPC-lipo targeted against vascular cell adhesion molecule (VCAM)-1 in the same animal model. The MRI findings were validated using fluorescence microscopy. Hence, liposomal citicoline represents a prototype theranostic system, where the therapeutic agent can be detected directly by CEST MRI in a label-free fashion.

Original languageEnglish (US)
Pages (from-to)1588-1600
Number of pages13
JournalTheranostics
Volume6
Issue number10
DOIs
StatePublished - 2016

Fingerprint

Cytidine Diphosphate Choline
Liposomes
Stroke
Pharmaceutical Preparations
Ischemia
Vascular Cell Adhesion Molecule-1
Middle Cerebral Artery Infarction
Brain
Neuroprotective Agents
Blood-Brain Barrier
Fluorescence Microscopy
Neurodegenerative Diseases
Hydroxyl Radical
Amines
Protons
Animal Models
6-chloro-3,5-diaminopyrazine-3-carboxamide

Keywords

  • CEST MRI
  • Citicoline
  • Ischemia
  • Liposome
  • Stroke
  • Theranostic

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)

Cite this

Label-free CEST MRI detection of citicoline-liposome drug delivery in ischemic stroke. / Liu, Huanling; Jablonska, Anna; Li, Yuguo; Cao, Suyi; Liu, Dexiang; Chen, Hanwei; Van Zijl, Peter C; Bulte, Jeff W; Janowski, Miroslaw; Walczak, Piotr; Liu, Guanshu.

In: Theranostics, Vol. 6, No. 10, 2016, p. 1588-1600.

Research output: Contribution to journalArticle

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abstract = "Citicoline (CDPC) is a natural supplement with well-documented neuroprotective effects in the treatment of neurodegenerative diseases. In the present study, we sought to exploit citicoline as a theranostic agent with its inherent chemical exchange saturation transfer (CEST) MRI signal, which can be directly used as an MRI guidance in the citicoline drug delivery. Our in vitro CEST MRI results showed citicoline has two inherent CEST signals at +1 and +2 ppm, attributed to exchangeable hydroxyl and amine protons, respectively. To facilitate the targeted drug delivery of citicoline to ischemic regions, we prepared liposomes encapsulating citicoline (CDPC-lipo) and characterized the particle properties and CEST MRI properties. The in vivo CEST MRI detection of liposomal citicoline was then examined in a rat brain model of unilateral transient ischemia induced by a two-hour middle cerebral artery occlusion. The results showed that the delivery of CPDC-lipo to the brain ischemic areas could be monitored and quantified by CEST MRI. When administered intra-arterially, CDPC-lipo clearly demonstrated a detectable CEST MRI contrast at 2 ppm. CEST MRI revealed that liposomes preferentially accumulated in the areas of ischemia with a disrupted blood-brain-barrier. We furthermore used CEST MRI to detect the improvement in drug delivery using CDPC-lipo targeted against vascular cell adhesion molecule (VCAM)-1 in the same animal model. The MRI findings were validated using fluorescence microscopy. Hence, liposomal citicoline represents a prototype theranostic system, where the therapeutic agent can be detected directly by CEST MRI in a label-free fashion.",
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