title: Ablative Focused Ultrasound Synergistically Enhances Thermally Triggered Chemotherapy for Prostate Cancer in Vitro.
abstract: High-intensity focused ultrasound (HIFU) can locally ablate biological tissues such as tumors, i.e., induce their rapid heating and coagulative necrosis without causing damage to surrounding healthy structures. It is widely used in clinical practice for minimally invasive treatment of prostate cancer. Nonablative, low-power HIFU was established as a promising tool for triggering the release of chemotherapeutic drugs from temperature-sensitive liposomes (TSLs). In this study, we combine ablative HIFU and thermally triggered chemotherapy to address the lack of safe and effective treatment options for elderly patients with high-risk localized prostate cancer. DU145 prostate cancer cells were exposed to chemotherapy (free and liposomal Sorafenib) and ablative HIFU, alone or in combination. Prior to cell viability assessment by trypan blue exclusion and flow cytometry, the uptake of TSLs by DU145 cells was verified by confocal microscopy and cryogenic scanning electron microscopy (cryo-SEM). The combination of TSLs encapsulating 10 μM Sorafenib and 8.7W HIFU resulted in a viability of less than 10% at 72 h post-treatment, which was significant less than the viability of the cells treated with free Sorafenib (76%), Sorafenib-loaded TSLs (63%), or HIFU alone (44%). This synergy was not observed on cells treated with Sorafenib-loaded nontemperature sensitive liposomes and HIFU. According to cryo-SEM analysis, cells exposed to ablative HIFU exhibited significant mechanical disruption. Water bath immersion experiments also showed an important role of mechanical effects in the synergistic enhancement of TSL-mediated chemotherapy by ablative HIFU. This combination therapy can be an effective strategy for treatment of geriatric prostate cancer patients.
authors.affiliation: Department of Chemical and Biomolecular Engineering, Tulane University , New Orleans, Louisiana 70118, United States.|Vector-Borne Infectious Disease Research Center, Tulane University , New Orleans, Louisiana 70118, United States.
authors.forename: Jaspreet S
authors.initials: JS
authors.lastname: Arora
authors.affiliation: Department of Biomedical Engineering, Tulane University , New Orleans, Louisiana 70118, United States.|Tulane Institute for Integrative Engineering for Health and Medicine, Tulane University , New Orleans, Louisiana 70118, United States.
authors.forename: Hakm Y
authors.initials: HY
authors.lastname: Murad
authors.affiliation: Department of Chemical and Biomolecular Engineering, Tulane University , New Orleans, Louisiana 70118, United States.
authors.forename: Stephen
authors.initials: S
authors.lastname: Ashe
authors.affiliation: Department of Biomedical Engineering, Tulane University , New Orleans, Louisiana 70118, United States.|Tulane Institute for Integrative Engineering for Health and Medicine, Tulane University , New Orleans, Louisiana 70118, United States.
authors.forename: Gray
authors.initials: G
authors.lastname: Halliburton
authors.affiliation: Department of Biomedical Engineering, Tulane University , New Orleans, Louisiana 70118, United States.|Tulane Institute for Integrative Engineering for Health and Medicine, Tulane University , New Orleans, Louisiana 70118, United States.
authors.forename: Heng
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Chemical and Biomolecular Engineering, Tulane University , New Orleans, Louisiana 70118, United States.
authors.forename: Jibao
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Chemical and Biomolecular Engineering, Tulane University , New Orleans, Louisiana 70118, United States.|Vector-Borne Infectious Disease Research Center, Tulane University , New Orleans, Louisiana 70118, United States.
authors.forename: Vijay T
authors.initials: VT
authors.lastname: John
authors.affiliation: Department of Biomedical Engineering, Tulane University , New Orleans, Louisiana 70118, United States.|Tulane Institute for Integrative Engineering for Health and Medicine, Tulane University , New Orleans, Louisiana 70118, United States.|Tulane Cancer Center, Tulane University School of Medicine , New Orleans, Louisiana 70118, United States.
authors.forename: Damir B
authors.initials: DB
authors.lastname: Khismatullin
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003131:Combined Modality Therapy; D020285:Cryoelectron Microscopy; D016503:Drug Delivery Systems / Q000379:methods; D057086:High-Intensity Focused Ultrasound Ablation / Q000379:methods*; D006801:Humans; D008081:Liposomes / Q000737:chemistry; D008297:Male; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000737:chemistry / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000628:therapy*; D000077157:Sorafenib
chemical_list: D008081:Liposomes; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib
keywords: Sorafenib; chemotherapy; high-intensity focused ultrasound (HIFU); prostate cancer; temperature-sensitive liposome (TSL); tumor ablation