Ultrasound-mediated tumor imaging and nanotherapy using drug loaded, block copolymer stabilized perfluorocarbon nanoemulsions

Natalya Rapoport, Kweon Ho Nam, Roohi Gupta, Zhongao Gao, Praveena Mohan, Allison Payne, Nick Todd, Xin Liu, Taeho Kim, Jill Shea, Courtney Scaife, Dennis L. Parker, Eun Kee Jeong, Anne M. Kennedy

Research output: Contribution to journalArticle

276 Scopus citations

Abstract

Perfluorocarbon nanoemulsions can deliver lipophilic therapeutic agents to solid tumors and simultaneously provide for monitoring nanocarrier biodistribution via ultrasonography and/or 19F MRI. In the first generation of block copolymer stabilized perfluorocarbon nanoemulsions, perfluoropentane (PFP) was used as the droplet forming compound. Although manifesting excellent therapeutic and ultrasound imaging properties, PFP nanoemulsions were unstable at storage, difficult to handle, and underwent hard to control phenomenon of irreversible droplet-to-bubble transition upon injection. To solve the above problems, perfluoro-15-crown-5-ether (PFCE) was used as a core forming compound in the second generation of block copolymer stabilized perfluorocarbon nanoemulsions. PFCE nanodroplets manifest both ultrasound and fluorine (19F) MR contrast properties, which allows using multimodal imaging and 19F MR spectroscopy for monitoring nanodroplet pharmacokinetics and biodistribution. In the present paper, acoustic, imaging, and therapeutic properties of unloaded and paclitaxel (PTX) loaded PFCE nanoemulsions are reported. As manifested by the 19F MR spectroscopy, PFCE nanodroplets are long circulating, with about 50% of the injected dose remaining in circulation 2 h after the systemic injection. Sonication with 1-MHz therapeutic ultrasound triggered reversible droplet-to-bubble transition in PFCE nanoemulsions. Microbubbles formed by acoustic vaporization of nanodroplets underwent stable cavitation. The nanodroplet size (200 nm to 350 nm depending on a type of the shell and conditions of emulsification) as well as long residence in circulation favored their passive accumulation in tumor tissue that was confirmed by ultrasonography. In the breast and pancreatic cancer animal models, ultrasound-mediated therapy with paclitaxel-loaded PFCE nanoemulsions showed excellent therapeutic properties characterized by tumor regression and suppression of metastasis. Anticipated mechanisms of the observed effects are discussed.

Original languageEnglish
Pages (from-to)4-15
Number of pages12
JournalJournal of Controlled Release
Volume153
Issue number1
DOIs
StatePublished - Jul 15 2011
Externally publishedYes

Keywords

  • Fluorine MRI
  • Fluorine MRS
  • Pancreatic cancer
  • Perfluorocarbon nanoemulsion
  • Ultrasonography
  • Ultrasound-mediated chemotherapy

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    Rapoport, N., Nam, K. H., Gupta, R., Gao, Z., Mohan, P., Payne, A., Todd, N., Liu, X., Kim, T., Shea, J., Scaife, C., Parker, D. L., Jeong, E. K., & Kennedy, A. M. (2011). Ultrasound-mediated tumor imaging and nanotherapy using drug loaded, block copolymer stabilized perfluorocarbon nanoemulsions. Journal of Controlled Release, 153(1), 4-15. https://doi.org/10.1016/j.jconrel.2011.01.022