Treating glioblastoma multiforme with selective high-dose liposomal doxorubicin chemotherapy induced by repeated focused ultrasound

Feng Yi Yang, Ming Che Teng, Maggie Lu, Hsiang Fa Liang, Yan Ru Lee, Chueh Chuan Yen, Muh Lii Liang, Tai-Tong Wong

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Background: High-dose tissue-specific delivery of therapeutic agents would be a valuable clinical strategy. We have previously shown that repeated transcranial focused ultrasound is able to increase the delivery of Evans blue significantly into brain tissue. The present study shows that repeated pulsed high-intensity focused ultrasound (HIFU) can be used to deliver high-dose atherosclerotic plaque-specific peptide-1 (AP-1)-conjugated liposomes selectively to brain tumors. Methods: Firefly luciferase (Fluc)-labeled human GBM8401 glioma cells were implanted into NOD-scid mice. AP-1-conjugated liposomal doxorubicin or liposomal doxorubicin alone was administered followed by pulsed HIFU and the doxorubicin concentration in the treated brains quantified by fluorometer. Growth of the labeled glioma cells was monitored through noninvasive bioluminescence imaging and finally the brain tissue was histologically examined after sacrifice. Results: Compared with the control group, the animals treated with 5 mg/kg injections of AP-1 liposomal doxorubicin or untargeted liposomal doxorubicin followed by repeated pulsed HIFU not only showed significantly enhanced accumulation of drug at the sonicated tumor site but also a significantly elevated tumor-to-normal brain drug ratio (P < 0.001). Combining repeated pulsed HIFU with AP-1 liposomal doxorubicin or untargeted liposomal doxorubicin has similar antitumor effects. Conclusion: This study demonstrates that targeted or untargeted liposomal doxorubicin, followed by repeated pulsed HIFU, is a promising high-dose chemotherapy method that allows the desired brain tumor region to be targeted specifically. 2012 Cárdenas et al, publisher and licensee Dove Medical Press Ltd.

Original languageEnglish
Pages (from-to)965-974
Number of pages10
JournalInternational Journal of Nanomedicine
Volume7
DOIs
Publication statusPublished - Dec 5 2012
Externally publishedYes

Fingerprint

Chemotherapy
Glioblastoma
Brain
Ultrasonics
Drug Therapy
Transcription Factor AP-1
Tumors
Tissue
Brain Neoplasms
Glioma
Fluorometers
Bioluminescence
Liposomes
Firefly Luciferases
Evans Blue
Inbred NOD Mouse
Peptides
Atherosclerotic Plaques
liposomal doxorubicin
Neuroimaging

Keywords

  • Blood-brain barrier
  • Brain tumor
  • Interleukin-4 receptor
  • Repeated focused ultrasound
  • Target drug delivery

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Biomaterials
  • Organic Chemistry
  • Drug Discovery

Cite this

Treating glioblastoma multiforme with selective high-dose liposomal doxorubicin chemotherapy induced by repeated focused ultrasound. / Yang, Feng Yi; Teng, Ming Che; Lu, Maggie; Liang, Hsiang Fa; Lee, Yan Ru; Yen, Chueh Chuan; Liang, Muh Lii; Wong, Tai-Tong.

In: International Journal of Nanomedicine, Vol. 7, 05.12.2012, p. 965-974.

Research output: Contribution to journalArticle

Yang, Feng Yi ; Teng, Ming Che ; Lu, Maggie ; Liang, Hsiang Fa ; Lee, Yan Ru ; Yen, Chueh Chuan ; Liang, Muh Lii ; Wong, Tai-Tong. / Treating glioblastoma multiforme with selective high-dose liposomal doxorubicin chemotherapy induced by repeated focused ultrasound. In: International Journal of Nanomedicine. 2012 ; Vol. 7. pp. 965-974.
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