Document Detail


Ultrasound-mediated tumor imaging and nanotherapy using drug loaded, block copolymer stabilized perfluorocarbon nanoemulsions.
MedLine Citation:
PMID:  21277919     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Perfluorocarbon nanoemulsions can deliver lipophilic therapeutic agents to solid tumors and simultaneously provide for monitoring nanocarrier biodistribution via ultrasonography and/or (19)F 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 ((19)F) MR contrast properties, which allows using multimodal imaging and (19)F 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 (19)F MR spectroscopy, PFCE nanodroplets are long circulating, with about 50% of the injected dose remaining in circulation 2h 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 (200nm to 350nm 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.
Authors:
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
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-01-26
Journal Detail:
Title:  Journal of controlled release : official journal of the Controlled Release Society     Volume:  153     ISSN:  1873-4995     ISO Abbreviation:  J Control Release     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-07-11     Completed Date:  2011-11-14     Revised Date:  2014-09-22    
Medline Journal Info:
Nlm Unique ID:  8607908     Medline TA:  J Control Release     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  4-15     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier B.V. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents, Phytogenic / administration & dosage*,  therapeutic use
Breast Neoplasms / therapy,  ultrasonography
Cell Line, Tumor
Drug Delivery Systems / methods*
Emulsions / chemistry
Female
Fluorocarbons / chemistry*
Humans
Mice
Nanomedicine / methods
Neoplasms / therapy*,  ultrasonography*
Paclitaxel / administration & dosage*,  therapeutic use
Pancreatic Neoplasms / therapy,  ultrasonography
Ultrasonic Therapy / methods*
Grant Support
ID/Acronym/Agency:
R01 EB001033/EB/NIBIB NIH HHS; R01 EB001033-09/EB/NIBIB NIH HHS; R01 EB001033-10/EB/NIBIB NIH HHS; R01EB001033/EB/NIBIB NIH HHS; R56 EB001033/EB/NIBIB NIH HHS; R56 EB001033-08A1/EB/NIBIB NIH HHS; R56EB001033/EB/NIBIB NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 0/Emulsions; 0/Fluorocarbons; 33069-62-4/Paclitaxel
Comments/Corrections

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