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Design and evaluation of doxorubicin-containing microbubbles for ultrasound-triggered doxorubicin delivery: cytotoxicity and mechanisms involved

Ine Lentacker (UGent) , Bart Geers (UGent) , Jo Demeester (UGent) , Stefaan De Smedt (UGent) and Niek Sanders (UGent)
(2010) MOLECULAR THERAPY. 18(1). p.101-108
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Abstract
Drug delivery with microbubbles and ultrasound is gaining more and more attention in the drug delivery field due to its noninvasiveness, local applicability, and proven safety in ultrasonic imaging techniques. In this article, we tried to improve the cytotoxicity of doxorubicin (DOX)-containing liposomes by preparing DOX-liposome-containing microbubbles for drug delivery with therapeutic ultrasound. In this way, the DOX release and uptake can be restricted to ultrasound-treated areas. Compared to DOX-liposomes, DOX-loaded microbubbles killed at least two times more melanoma cells after exposure to ultrasound. After treatment of the melanoma cells with DOX-liposome-loaded microbubbles and ultrasound, DOX was mainly present in the nuclei of the cancer cells, whereas it was mainly detected in the cytoplasm of cells treated with DOX-liposomes. Exposure of cells to DOX-liposome-loaded microbubbles and ultrasound caused an almost instantaneous cellular entry of the DOX. At least two mechanisms were identified that explain the fast uptake of DOX and the superior cell killing of DOX-liposome-loaded microbubbles and ultrasound. First, exposure of DOX-liposome-loaded microbubbles to ultrasound results in the release of free DOX that is more cytotoxic than DOX-liposomes. Second, the cellular entry of the released DOX is facilitated due to sonoporation of the cell membranes. The in vitro results shown in this article indicate that DOX-liposome-loaded microbubbles could be a very interesting tool to obtain an efficient ultrasound-controlled DOX delivery in vivo.
Keywords
CAVITATION, EXPOSURE, CHEMOTHERAPY, CELLS, GENE DELIVERY, CONTRAST AGENTS, IN-VITRO, CANCER-THERAPY, MICELLAR-ENCAPSULATED DRUG, LIPOPLEX-LOADED MICROBUBBLES

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Please use this url to cite or link to this publication:

Chicago
Lentacker, Ine, Bart Geers, Jo Demeester, Stefaan De Smedt, and Niek Sanders. 2010. “Design and Evaluation of Doxorubicin-containing Microbubbles for Ultrasound-triggered Doxorubicin Delivery: Cytotoxicity and Mechanisms Involved.” Molecular Therapy 18 (1): 101–108.
APA
Lentacker, I., Geers, B., Demeester, J., De Smedt, S., & Sanders, N. (2010). Design and evaluation of doxorubicin-containing microbubbles for ultrasound-triggered doxorubicin delivery: cytotoxicity and mechanisms involved. MOLECULAR THERAPY, 18(1), 101–108.
Vancouver
1.
Lentacker I, Geers B, Demeester J, De Smedt S, Sanders N. Design and evaluation of doxorubicin-containing microbubbles for ultrasound-triggered doxorubicin delivery: cytotoxicity and mechanisms involved. MOLECULAR THERAPY. 2010;18(1):101–8.
MLA
Lentacker, Ine, Bart Geers, Jo Demeester, et al. “Design and Evaluation of Doxorubicin-containing Microbubbles for Ultrasound-triggered Doxorubicin Delivery: Cytotoxicity and Mechanisms Involved.” MOLECULAR THERAPY 18.1 (2010): 101–108. Print.
@article{1849829,
  abstract     = {Drug delivery with microbubbles and ultrasound is gaining more and more attention in the drug delivery field due to its noninvasiveness, local applicability, and proven safety in ultrasonic imaging techniques. In this article, we tried to improve the cytotoxicity of doxorubicin (DOX)-containing liposomes by preparing DOX-liposome-containing microbubbles for drug delivery with therapeutic ultrasound. In this way, the DOX release and uptake can be restricted to ultrasound-treated areas. Compared to DOX-liposomes, DOX-loaded microbubbles killed at least two times more melanoma cells after exposure to ultrasound. After treatment of the melanoma cells with DOX-liposome-loaded microbubbles and ultrasound, DOX was mainly present in the nuclei of the cancer cells, whereas it was mainly detected in the cytoplasm of cells treated with DOX-liposomes. Exposure of cells to DOX-liposome-loaded microbubbles and ultrasound caused an almost instantaneous cellular entry of the DOX. At least two mechanisms were identified that explain the fast uptake of DOX and the superior cell killing of DOX-liposome-loaded microbubbles and ultrasound. First, exposure of DOX-liposome-loaded microbubbles to ultrasound results in the release of free DOX that is more cytotoxic than DOX-liposomes. Second, the cellular entry of the released DOX is facilitated due to sonoporation of the cell membranes. The in vitro results shown in this article indicate that DOX-liposome-loaded microbubbles could be a very interesting tool to obtain an efficient ultrasound-controlled DOX delivery in vivo.},
  author       = {Lentacker, Ine and Geers, Bart and Demeester, Jo and De Smedt, Stefaan and Sanders, Niek},
  issn         = {1525-0016},
  journal      = {MOLECULAR THERAPY},
  keyword      = {CAVITATION,EXPOSURE,CHEMOTHERAPY,CELLS,GENE DELIVERY,CONTRAST AGENTS,IN-VITRO,CANCER-THERAPY,MICELLAR-ENCAPSULATED DRUG,LIPOPLEX-LOADED MICROBUBBLES},
  language     = {eng},
  number       = {1},
  pages        = {101--108},
  title        = {Design and evaluation of doxorubicin-containing microbubbles for ultrasound-triggered doxorubicin delivery: cytotoxicity and mechanisms involved},
  url          = {http://dx.doi.org/10.1038/mt.2009.160},
  volume       = {18},
  year         = {2010},
}

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