1. Short-time focused ultrasound hyperthermia enhances liposomal doxorubicin delivery and antitumor efficacy for brain metastasis of breast cancer
- Author
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Tzu-Hung Lin, Win-Li Lin, Chi-Feng Chiang, Houng-Chi Liou, Yu-Hone Hsu, Wen-Mei Fu, and Sheng-Kai Wu
- Subjects
Hyperthermia ,Pathology ,medicine.medical_specialty ,focused ultrasound (FUS) ,Ultrasonic Therapy ,Biophysics ,Pharmaceutical Science ,Antineoplastic Agents ,Apoptosis ,Breast Neoplasms ,Bioengineering ,Polyethylene Glycols ,Biomaterials ,Mice ,Breast cancer ,International Journal of Nanomedicine ,Cell Line, Tumor ,brain metastasis of breast cancer ,Drug Discovery ,In Situ Nick-End Labeling ,medicine ,Animals ,Doxorubicin ,Cell Proliferation ,Original Research ,Drug Carriers ,Mice, Inbred BALB C ,Microbubbles ,Brain Neoplasms ,Cell growth ,business.industry ,Organic Chemistry ,Brain ,Hyperthermia, Induced ,General Medicine ,hyperthermia ,medicine.disease ,Cancer research ,Nanoparticles ,Immunohistochemistry ,Female ,lipids (amino acids, peptides, and proteins) ,business ,pegylated liposomal doxorubicin (PLD) ,medicine.drug ,Brain metastasis - Abstract
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
- Published
- 2014