Malignant brain tumors remain difficult to treat with chemotherapy because the blood–brain barrier (BBB) limits the amounts of potent agents that can reach the tumor, such that the drugs are unable to reach therapeutic dosage. Although various targeted carriers that encapsulate chemotherapeutic agents have been shown to improve drug delivery to brain tumors, the BBB is still a major obstacle in the use of chemotherapy for the treatment of these tumors. Human glioblastoma-bearing mice were injected intravenously with doxorubicin (Dox) encapsulated in atherosclerotic plaque-specific peptide-1 (AP-1)-conjugated liposomes or unconjugated liposome. These treatments took place with or without BBB disruption induced by transcranial pulsed high-intensity focused ultrasound (pulsed HIFU). This study showed that the treatment with Dox encapsulated in AP-1-conjugated liposomes followed by pulsed HIFU enhanced the accumulation of the cytotoxic drug in cells and inhibited the growth of brain tumors in vivo. Combining pulsed HIFU with cytotoxic agents might improve their efficacy in patients with brain tumors while simultaneously reducing the drug side effects. Further investigation is required to provide a comprehensive physical characterization of the sonication process and to determine its bioeffects.
 R. Barth, et al., "Boron neutron capture therapy of brain tumors: enhanced survival following intracarotid injection of either sodium borocaptate or boronophenylalanine with or without blood-brain barrier disruption," Cancer Research, vol. 57, p. 1129, 1997.
 R. F. Barth, et al., "Neutron capture therapy of intracerebral melanoma: enhanced survival and cure after blood-brain barrier opening to improve delivery of boronophenylalanine," Int J Radiat Oncol Biol Phys, vol. 52, pp. 858-68, Mar 1 2002.
 C. H. Hsieh, et al., "Evaluation of pharmacokinetics of 4-borono-2-(18)F-fluoro-L-phenylalanine for boron neutron capture therapy in a glioma-bearing rat model with hyperosmolar blood-brain barrier disruption," J Nucl Med, vol. 46, pp. 1858-65, Nov 2005.
 D. F. Deen, et al., "Brain Tumor Working Group Report on the 9th International Conference on Brain Tumor Research and Therapy. Organ System Program, National Cancer Institute," J Neurooncol, vol. 16, pp. 243-72, Jun 1993.
 R. J. Motzer, et al., "Phase II trial of high-dose carboplatin and etoposide with autologous bone marrow transplantation in first-line therapy for patients with poor-risk germ cell tumors," J Natl Cancer Inst, vol. 85, pp. 1828-35, Nov 17 1993.
 R. J. Motzer, et al., "High-dose carboplatin, etoposide, and cyclophosphamide with autologous bone marrow transplantation in first-line therapy for patients with poor-risk germ cell tumors," J Clin Oncol, vol. 15, pp. 2546-52, Jul 1997.
 R. K. Puri, et al., "Human neurological cancer cells express interleukin-4 (IL-4) receptors which are targets for the toxic effects of IL4-Pseudomonas exotoxin chimeric protein," Int J Cancer, vol. 58, pp. 574-81, Aug 15 1994.
 H. Y. Hong, et al., "Phage display selection of peptides that home to atherosclerotic plaques: IL-4 receptor as a candidate target in atherosclerosis," J Cell Mol Med, vol. 12, pp. 2003-14, Oct 2008.