Noninvasive drug delivery using ultrasound: Targeting melanoma using siRNA against mutant (V600E) B-Raf

Melissa A. Tran, Raghavendra Gowda, Eun Joo Park, James Adair, Nadine Smith, Mark Kester, Gavin P. Robertson

Research output: Chapter in Book/Report/Conference proceedingConference contribution

4 Citations (Scopus)

Abstract

Melanoma is the most deadly form of skin cancer. Currently early surgical removal is the best treatment option for melanoma patients with little hope of successful treatment of late stage melanoma. Clearly new treatment options must be explored. Topical administration of drugs provides the advantage of being able to apply large quantities of drug in close proximity to the tumor without the issue of systemic side effects. However, the natural barrier formed by the skin must first be overcome for topical treatment to become a viable option. With this in mind we have sought to use low-frequency ultrasound to transiently permeabilize the stratum corneum and successfully deliver liposomal siRNA to melanoma cells residing at the basement membrane. B-Raf is one of the most frequently activated genes in melanoma, making it an ideal candidate for targeting via siRNA. The novel liposomes used in this study load siRNA, protect if from the outside environment and lead to knockdown of target message. Combining ultrasound with liposomal siRNA we show that siRNA can be delivered into melanoma cells. Additionally, we show that siRNA to mutant B-Raf can effectively inhibit melanoma growth in reconstructs and in mice by 60% and 30% respectively. Therefore, ultrasound with liposomal siRNA is a potentially valuable treatment option for melanoma patients.

Original languageEnglish (US)
Title of host publication8th International Symposium on Therapeutic Ultrasound
Pages423-427
Number of pages5
DOIs
StatePublished - Jul 21 2009
Event8th International Symposium on Therapeutic Ultrasound - Minneapolis, MN, United States
Duration: Sep 10 2008Sep 13 2008

Publication series

NameAIP Conference Proceedings
Volume1113
ISSN (Print)0094-243X
ISSN (Electronic)1551-7616

Other

Other8th International Symposium on Therapeutic Ultrasound
CountryUnited States
CityMinneapolis, MN
Period9/10/089/13/08

Fingerprint

delivery
drugs
cornea
strata
messages
cells
basements
genes
mice
proximity
tumors
cancer
membranes
low frequencies

All Science Journal Classification (ASJC) codes

  • Physics and Astronomy(all)

Cite this

Tran, M. A., Gowda, R., Park, E. J., Adair, J., Smith, N., Kester, M., & Robertson, G. P. (2009). Noninvasive drug delivery using ultrasound: Targeting melanoma using siRNA against mutant (V600E) B-Raf. In 8th International Symposium on Therapeutic Ultrasound (pp. 423-427). (AIP Conference Proceedings; Vol. 1113). https://doi.org/10.1063/1.3131463
Tran, Melissa A. ; Gowda, Raghavendra ; Park, Eun Joo ; Adair, James ; Smith, Nadine ; Kester, Mark ; Robertson, Gavin P. / Noninvasive drug delivery using ultrasound : Targeting melanoma using siRNA against mutant (V600E) B-Raf. 8th International Symposium on Therapeutic Ultrasound. 2009. pp. 423-427 (AIP Conference Proceedings).
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title = "Noninvasive drug delivery using ultrasound: Targeting melanoma using siRNA against mutant (V600E) B-Raf",
abstract = "Melanoma is the most deadly form of skin cancer. Currently early surgical removal is the best treatment option for melanoma patients with little hope of successful treatment of late stage melanoma. Clearly new treatment options must be explored. Topical administration of drugs provides the advantage of being able to apply large quantities of drug in close proximity to the tumor without the issue of systemic side effects. However, the natural barrier formed by the skin must first be overcome for topical treatment to become a viable option. With this in mind we have sought to use low-frequency ultrasound to transiently permeabilize the stratum corneum and successfully deliver liposomal siRNA to melanoma cells residing at the basement membrane. B-Raf is one of the most frequently activated genes in melanoma, making it an ideal candidate for targeting via siRNA. The novel liposomes used in this study load siRNA, protect if from the outside environment and lead to knockdown of target message. Combining ultrasound with liposomal siRNA we show that siRNA can be delivered into melanoma cells. Additionally, we show that siRNA to mutant B-Raf can effectively inhibit melanoma growth in reconstructs and in mice by 60{\%} and 30{\%} respectively. Therefore, ultrasound with liposomal siRNA is a potentially valuable treatment option for melanoma patients.",
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Tran, MA, Gowda, R, Park, EJ, Adair, J, Smith, N, Kester, M & Robertson, GP 2009, Noninvasive drug delivery using ultrasound: Targeting melanoma using siRNA against mutant (V600E) B-Raf. in 8th International Symposium on Therapeutic Ultrasound. AIP Conference Proceedings, vol. 1113, pp. 423-427, 8th International Symposium on Therapeutic Ultrasound, Minneapolis, MN, United States, 9/10/08. https://doi.org/10.1063/1.3131463

Noninvasive drug delivery using ultrasound : Targeting melanoma using siRNA against mutant (V600E) B-Raf. / Tran, Melissa A.; Gowda, Raghavendra; Park, Eun Joo; Adair, James; Smith, Nadine; Kester, Mark; Robertson, Gavin P.

8th International Symposium on Therapeutic Ultrasound. 2009. p. 423-427 (AIP Conference Proceedings; Vol. 1113).

Research output: Chapter in Book/Report/Conference proceedingConference contribution

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Tran MA, Gowda R, Park EJ, Adair J, Smith N, Kester M et al. Noninvasive drug delivery using ultrasound: Targeting melanoma using siRNA against mutant (V600E) B-Raf. In 8th International Symposium on Therapeutic Ultrasound. 2009. p. 423-427. (AIP Conference Proceedings). https://doi.org/10.1063/1.3131463