Short-time focused ultrasound hyperthermia enhances liposomal doxorubicin delivery and antitumor efficacy for brain metastasis of breast cancer
Sheng-Kai Wu,1 Chi-Feng Chiang,1 Yu-Hone Hsu,1,4 Tzu-Hung Lin,2 Houng-Chi Liou,2 Wen-Mei Fu,2 Win-Li Lin1,3 1Institute of Biomedical Engineering, College of Medicine and College of Engineering, 2Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan; 3Institute...
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Dove Medical Press
2014
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oai:doaj.org-article:8c3a82babf2846d4b9b11bd16130038d2021-12-02T06:32:31ZShort-time focused ultrasound hyperthermia enhances liposomal doxorubicin delivery and antitumor efficacy for brain metastasis of breast cancer1178-2013https://doaj.org/article/8c3a82babf2846d4b9b11bd16130038d2014-09-01T00:00:00Zhttp://www.dovepress.com/short-time-focused-ultrasound-hyperthermia-enhances-liposomal-doxorubi-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 Sheng-Kai Wu,1 Chi-Feng Chiang,1 Yu-Hone Hsu,1,4 Tzu-Hung Lin,2 Houng-Chi Liou,2 Wen-Mei Fu,2 Win-Li Lin1,3 1Institute of Biomedical Engineering, College of Medicine and College of Engineering, 2Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan; 3Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli, Taiwan; 4Department of Neurosurgery, Cheng-Hsin General Hospital, Taipei, Taiwan Abstract: The blood–brain/tumor barrier inhibits the uptake and accumulation of chemotherapeutic drugs. Hyperthermia can enhance the delivery of chemotherapeutic agent into tumors. In this study, we investigated the effects of short-time focused ultrasound (FUS) hyperthermia on the delivery and therapeutic efficacy of pegylated liposomal doxorubicin (PLD) for brain metastasis of breast cancer. Murine breast cancer 4T1-luc2 cells expressing firefly luciferase were injected into female BALB/c mice striatum tissues and used as a brain metastasis model. The mice were intravenously injected with PLD (5 mg/kg) with/without 10-minute transcranial FUS hyperthermia on day 6 after tumor implantation. The amounts of doxorubicin accumulated in the normal brain tissues and tumor tissues with/without FUS hyperthermia were measured using fluorometry. The tumor growth for the control, hyperthermia, PLD, and PLD + hyperthermia groups was measured using an IVIS spectrum system every other day from day 3 to day 11. Cell apoptosis and tumor characteristics were assessed using immunohistochemistry. Short-time FUS hyperthermia was able to significantly enhance the PLD delivery into brain tumors. The tumor growth was effectively inhibited by a single treatment of PLD + hyperthermia compared with both PLD alone and short-time FUS hyperthermia alone. Immunohistochemical examination further demonstrated the therapeutic efficacy of PLD plus short-time FUS hyperthermia for brain metastasis of breast cancer. The application of short-time FUS hyperthermia after nanodrug injection may be an effective approach to enhance nanodrug delivery and improve the treatment of metastatic cancers. Keywords: hyperthermia, focused ultrasound (FUS), pegylated liposomal doxorubicin (PLD), brain metastasis of breast cancerWu SKChiang CFHsu YHLin THLiou HCFu WMLin WLDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 4485-4494 (2014) |
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Medicine (General) R5-920 Wu SK Chiang CF Hsu YH Lin TH Liou HC Fu WM Lin WL Short-time focused ultrasound hyperthermia enhances liposomal doxorubicin delivery and antitumor efficacy for brain metastasis of breast cancer |
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Sheng-Kai Wu,1 Chi-Feng Chiang,1 Yu-Hone Hsu,1,4 Tzu-Hung Lin,2 Houng-Chi Liou,2 Wen-Mei Fu,2 Win-Li Lin1,3 1Institute of Biomedical Engineering, College of Medicine and College of Engineering, 2Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan; 3Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli, Taiwan; 4Department of Neurosurgery, Cheng-Hsin General Hospital, Taipei, Taiwan Abstract: The blood–brain/tumor barrier inhibits the uptake and accumulation of chemotherapeutic drugs. Hyperthermia can enhance the delivery of chemotherapeutic agent into tumors. In this study, we investigated the effects of short-time focused ultrasound (FUS) hyperthermia on the delivery and therapeutic efficacy of pegylated liposomal doxorubicin (PLD) for brain metastasis of breast cancer. Murine breast cancer 4T1-luc2 cells expressing firefly luciferase were injected into female BALB/c mice striatum tissues and used as a brain metastasis model. The mice were intravenously injected with PLD (5 mg/kg) with/without 10-minute transcranial FUS hyperthermia on day 6 after tumor implantation. The amounts of doxorubicin accumulated in the normal brain tissues and tumor tissues with/without FUS hyperthermia were measured using fluorometry. The tumor growth for the control, hyperthermia, PLD, and PLD + hyperthermia groups was measured using an IVIS spectrum system every other day from day 3 to day 11. Cell apoptosis and tumor characteristics were assessed using immunohistochemistry. Short-time FUS hyperthermia was able to significantly enhance the PLD delivery into brain tumors. The tumor growth was effectively inhibited by a single treatment of PLD + hyperthermia compared with both PLD alone and short-time FUS hyperthermia alone. Immunohistochemical examination further demonstrated the therapeutic efficacy of PLD plus short-time FUS hyperthermia for brain metastasis of breast cancer. The application of short-time FUS hyperthermia after nanodrug injection may be an effective approach to enhance nanodrug delivery and improve the treatment of metastatic cancers. Keywords: hyperthermia, focused ultrasound (FUS), pegylated liposomal doxorubicin (PLD), brain metastasis of breast cancer |
format |
article |
author |
Wu SK Chiang CF Hsu YH Lin TH Liou HC Fu WM Lin WL |
author_facet |
Wu SK Chiang CF Hsu YH Lin TH Liou HC Fu WM Lin WL |
author_sort |
Wu SK |
title |
Short-time focused ultrasound hyperthermia enhances liposomal doxorubicin delivery and antitumor efficacy for brain metastasis of breast cancer |
title_short |
Short-time focused ultrasound hyperthermia enhances liposomal doxorubicin delivery and antitumor efficacy for brain metastasis of breast cancer |
title_full |
Short-time focused ultrasound hyperthermia enhances liposomal doxorubicin delivery and antitumor efficacy for brain metastasis of breast cancer |
title_fullStr |
Short-time focused ultrasound hyperthermia enhances liposomal doxorubicin delivery and antitumor efficacy for brain metastasis of breast cancer |
title_full_unstemmed |
Short-time focused ultrasound hyperthermia enhances liposomal doxorubicin delivery and antitumor efficacy for brain metastasis of breast cancer |
title_sort |
short-time focused ultrasound hyperthermia enhances liposomal doxorubicin delivery and antitumor efficacy for brain metastasis of breast cancer |
publisher |
Dove Medical Press |
publishDate |
2014 |
url |
https://doaj.org/article/8c3a82babf2846d4b9b11bd16130038d |
work_keys_str_mv |
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