Pulsed-wave low-dose ultrasound hyperthermia selectively enhances nanodrug delivery and improves antitumor efficacy for brain metastasis of breast cancer
Journal
Ultrasonics Sonochemistry
Journal Volume
36
Pages
198-205
Date Issued
2017
Author(s)
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: 500 kHz, PRF: 1000 Hz, 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. ? 2016 Elsevier B.V.
SDGs
Other Subjects
Brain; Cell death; Diseases; Histology; Mammals; Pathology; Programmable logic controllers; Ultrasonics; Brain tumor treatments; Brain tumors; Clinical application; Immunofluorescence staining; Liposomal doxorubicin; Low dose; Nanodrug; Pulsed wave; Tumors; doxorubicin; firefly luciferase; antineoplastic agent; doxorubicin; macrogol derivative; nanomaterial; animal experiment; animal model; animal tissue; antineoplastic activity; apoptosis; Article; brain metastasis; brain tissue; brain tumor; breast cancer; cancer transplantation; clinical effectiveness; clinical evaluation; controlled study; corpus striatum; drug delivery system; drug distribution; drug efficacy; echography; fluorometry; hyperthermia; immunofluorescence; in vitro study; mouse; nonhuman; priority journal; radiation dose; staining; tumor growth; ultrasound hyperthermia; ultrasound transducer; analogs and derivatives; animal; brain tumor; breast tumor; cell proliferation; chemistry; drug delivery system; drug effect; pathology; procedures; secondary; thermotherapy; tumor cell line; ultrasound; Animals; Antineoplastic Agents; Apoptosis; Brain Neoplasms; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Doxorubicin; Drug Delivery Systems; Hyperthermia, Induced; Mice; Nanostructures; Polyethylene Glycols; Ultrasonic Waves
Type
journal article