Pulsed-high intensity focused ultrasound and low temperature - Sensitive liposomes for enhanced targeted drug delivery and antitumor effect

Sergio Dromi, Victor Frenkel, Alfred Luk, Bryan Traughber, Mary Angstadt, Monica Bur, Jason Poff, Jianwu Xie, Steven K. Libutti, King C P Li, Bradford J. Wood

Research output: Contribution to journalArticle

331 Citations (Scopus)

Abstract

Purpose: To determine if pulsed-high intensity focused ultrasound (HIFU) could effectively serve as a source of hyperthermia with thermosensitive liposomes to enhance delivery and efficacy of doxorubicin in tumors. Experimental Design: Comparisons in vitro and in vivo were carried out between non-thermosensitive liposomes (NTSL) and low temperature - sensitive liposomes (LTSL). Liposomes were incubated in vitro over a range of temperatures and durations, and the amount of doxorubicin released was measured. For in vivo experiments, liposomes and free doxorubicin were injected i.v. in mice followed by pulsed-HIFU exposures in s.c. murine adenocarcinoma tumors at 0 and 24 h after administration. Combinations of the exposures and drug formulations were evaluated for doxorubicin concentration and growth inhibition in the tumors. Results: In vitro incubations simulating the pulsed-HIFU thermal dose (42°C for 2 min) triggered release of 50% of doxorubicin from the LTSLs; however, no detectable release from the NTSLs was observed. Similarly, in vivo experiments showed that pulsed-HIFU exposures combined with the LTSLs resulted in more rapid delivery of doxorubicin as well as significantly higher i.t. concentration when compared with LTSLs alone or NTSLs, with or without exposures. Combining the exposures with the LTSLs also significantly reduced tumor growth compared with all other groups. Conclusions: Combining low-temperature heat-sensitive liposomes with noninvasive and non-destructive pulsed-HIFU exposures enhanced the delivery of doxorubicin and, consequently, its antitumor effects. This combination therapy could potentially produce viable clinical strategies for improved targeting and delivery of drugs for treatment of cancer and other diseases.

Original languageEnglish (US)
Pages (from-to)2722-2727
Number of pages6
JournalClinical Cancer Research
Volume13
Issue number9
DOIs
StatePublished - May 1 2007
Externally publishedYes

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Liposomes
Antineoplastic Agents
Doxorubicin
Temperature
Neoplasms
Hot Temperature
Drug Compounding
Drug Delivery Systems
Growth
Adenocarcinoma
Research Design
Fever
Therapeutics
In Vitro Techniques

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Pulsed-high intensity focused ultrasound and low temperature - Sensitive liposomes for enhanced targeted drug delivery and antitumor effect. / Dromi, Sergio; Frenkel, Victor; Luk, Alfred; Traughber, Bryan; Angstadt, Mary; Bur, Monica; Poff, Jason; Xie, Jianwu; Libutti, Steven K.; Li, King C P; Wood, Bradford J.

In: Clinical Cancer Research, Vol. 13, No. 9, 01.05.2007, p. 2722-2727.

Research output: Contribution to journalArticle

Dromi, S, Frenkel, V, Luk, A, Traughber, B, Angstadt, M, Bur, M, Poff, J, Xie, J, Libutti, SK, Li, KCP & Wood, BJ 2007, 'Pulsed-high intensity focused ultrasound and low temperature - Sensitive liposomes for enhanced targeted drug delivery and antitumor effect', Clinical Cancer Research, vol. 13, no. 9, pp. 2722-2727. https://doi.org/10.1158/1078-0432.CCR-06-2443
Dromi, Sergio ; Frenkel, Victor ; Luk, Alfred ; Traughber, Bryan ; Angstadt, Mary ; Bur, Monica ; Poff, Jason ; Xie, Jianwu ; Libutti, Steven K. ; Li, King C P ; Wood, Bradford J. / Pulsed-high intensity focused ultrasound and low temperature - Sensitive liposomes for enhanced targeted drug delivery and antitumor effect. In: Clinical Cancer Research. 2007 ; Vol. 13, No. 9. pp. 2722-2727.
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abstract = "Purpose: To determine if pulsed-high intensity focused ultrasound (HIFU) could effectively serve as a source of hyperthermia with thermosensitive liposomes to enhance delivery and efficacy of doxorubicin in tumors. Experimental Design: Comparisons in vitro and in vivo were carried out between non-thermosensitive liposomes (NTSL) and low temperature - sensitive liposomes (LTSL). Liposomes were incubated in vitro over a range of temperatures and durations, and the amount of doxorubicin released was measured. For in vivo experiments, liposomes and free doxorubicin were injected i.v. in mice followed by pulsed-HIFU exposures in s.c. murine adenocarcinoma tumors at 0 and 24 h after administration. Combinations of the exposures and drug formulations were evaluated for doxorubicin concentration and growth inhibition in the tumors. Results: In vitro incubations simulating the pulsed-HIFU thermal dose (42°C for 2 min) triggered release of 50{\%} of doxorubicin from the LTSLs; however, no detectable release from the NTSLs was observed. Similarly, in vivo experiments showed that pulsed-HIFU exposures combined with the LTSLs resulted in more rapid delivery of doxorubicin as well as significantly higher i.t. concentration when compared with LTSLs alone or NTSLs, with or without exposures. Combining the exposures with the LTSLs also significantly reduced tumor growth compared with all other groups. Conclusions: Combining low-temperature heat-sensitive liposomes with noninvasive and non-destructive pulsed-HIFU exposures enhanced the delivery of doxorubicin and, consequently, its antitumor effects. This combination therapy could potentially produce viable clinical strategies for improved targeting and delivery of drugs for treatment of cancer and other diseases.",
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AU - Frenkel, Victor

AU - Luk, Alfred

AU - Traughber, Bryan

AU - Angstadt, Mary

AU - Bur, Monica

AU - Poff, Jason

AU - Xie, Jianwu

AU - Libutti, Steven K.

AU - Li, King C P

AU - Wood, Bradford J.

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N2 - Purpose: To determine if pulsed-high intensity focused ultrasound (HIFU) could effectively serve as a source of hyperthermia with thermosensitive liposomes to enhance delivery and efficacy of doxorubicin in tumors. Experimental Design: Comparisons in vitro and in vivo were carried out between non-thermosensitive liposomes (NTSL) and low temperature - sensitive liposomes (LTSL). Liposomes were incubated in vitro over a range of temperatures and durations, and the amount of doxorubicin released was measured. For in vivo experiments, liposomes and free doxorubicin were injected i.v. in mice followed by pulsed-HIFU exposures in s.c. murine adenocarcinoma tumors at 0 and 24 h after administration. Combinations of the exposures and drug formulations were evaluated for doxorubicin concentration and growth inhibition in the tumors. Results: In vitro incubations simulating the pulsed-HIFU thermal dose (42°C for 2 min) triggered release of 50% of doxorubicin from the LTSLs; however, no detectable release from the NTSLs was observed. Similarly, in vivo experiments showed that pulsed-HIFU exposures combined with the LTSLs resulted in more rapid delivery of doxorubicin as well as significantly higher i.t. concentration when compared with LTSLs alone or NTSLs, with or without exposures. Combining the exposures with the LTSLs also significantly reduced tumor growth compared with all other groups. Conclusions: Combining low-temperature heat-sensitive liposomes with noninvasive and non-destructive pulsed-HIFU exposures enhanced the delivery of doxorubicin and, consequently, its antitumor effects. This combination therapy could potentially produce viable clinical strategies for improved targeting and delivery of drugs for treatment of cancer and other diseases.

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