Pulsed-wave low-dose ultrasound hyperthermia selectively enhances nanodrug delivery and improves antitumor efficacy for brain metastasis of breast cancer
Authors: Sheng-Kai Wu
Houng-Chi Liou
Yu-Hone Hsu
Chi-Feng Chiang
Win-Li Lin
Wen-Mei Fu
Journal: Ultrasonics Sonochemistry (2017)
Discipline: CHEMISTRY
Keywords: Brain tumors; Low-dose; Nanodrug; Pulsed-wave; Ultrasound hyperthermia.
Affiliations: Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan., Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan; Department of Neurosurgery, Cheng-Hsin General Hospital, Taipei, Taiwan., Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan., Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan; Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli, Taiwan. Electronic address: .

Abstract:  The clinical application of chemotherapeutics for brain tumors remains a challenge due to limitation of blood-brain barrier/blood-tumor barrier (BBB/BTB). In this study, we investigated the effects of low-dose focused ultrasound hyperthermia (UH) on the delivery and therapeutic efficacy of pegylated liposomal doxorubicin (PLD) for brain metastasis of breast cancer. Murine breast cancer cells (4T1-luc2) expressing firefly luciferase were implanted into mouse striatum as a brain tumor model. The mice were intravenously injected with PLD with/without transcranial pulsed-wave/continuous-wave UH (pUH/cUH) treatment on day-6 after tumor implantation. pUH (frequency: 500kHz, PRF: 1000Hz, duty cycle: 50%) was conducted under equal acoustic power (2.2-Watt) and sonication duration (10-min) as cUH. The amounts of doxorubicin accumulated in the normal brain and tumor tissues were measured with fluorometry. The tumor growth responses for the control, pUH, PLD, PLD+cUH, and PLD+pUH groups were evaluated with IVIS. The PLD distribution and cell apoptosis were assessed with immunofluorescence staining. The results showed that pUH significantly enhanced the PLD delivery into brain tumors and the tumor growth was further inhibited by PLD+pUH without damaging the sonicated normal brain tissues. This indicates that low-dose transcranial pUH is a promising method to selectively enhance nanodrug delivery and improve the brain tumor treatment. 

Retracted: No

PubPeer comments:
 Figure 3C of this paper appears to look very similar to Figure 3B of Soumya et al., (2012) Carbohydrate polymers, 87(2), 1787-1795.tDOI: 10.1016 j.carbpol.2011.09.094 (see: https: pubpeer.com publications F101132F6BA2EFF09969BB902482C4 . Could the authors please check? ![file] , 
 Corrigendum published [1 August 2019] . ------------------------------------------------ The authors regret for a mistake happened in the article. In the original manuscript, unfortunately we inserted wrong image in Fig. 3C. It has been rectified and the corrected Fig. 3 is presented below. ![] The authors would like to apologize for any inconvenience caused. ,