Focused Ultrasound-Triggered Release of Tyrosine Kinase Inhibitor From Thermosensitive Liposomes for Treatment of Renal Cell Carcinoma.
This study reports, for the first time, development of tyrosine kinase inhibitor-loaded, thermosensitive liposomes (TKI/TSLs) and their efficacy for treatment of renal cell carcinoma when triggered by focused ultrasound (FUS). Uptake of these nanoparticles into renal cancer cells was visualized with confocal and fluorescent imaging of rhodamine B-loaded liposomes. The combination of TKI/TSLs and FUS was tested in an in vitro tumor model of renal cell carcinoma. According to MTT cytotoxic assay and flow cytometric analysis, the combined treatment led to the least viability (23.4% ± 2.49%, p < 0.001), significantly lower than that observed from treatment with FUS (97.6% ± 0.67%, not significant) or TKI/TSL (71.0% ± 3.65%, p < 0.001) at 96 h compared to control. The importance of this unique, synergistic combination was demonstrated in viability experiments with non-thermosensitive liposomes (TKI/NTSL + FUS: 58.8% ± 1.5% vs. TKI/TSL + FUS: 36.2% ± 1.4%, p < 0.001) and heated water immersion (TKI/TSL + WB43°: 59.3% ± 2.91% vs. TKI/TSL + FUS: 36.4% ± 1.55%, p < 0.001). Our findings coupled with the existing use of FUS in clinical practice make the proposed combination of targeted chemotherapy, nanotechnology, and FUS a promising platform for enhanced drug delivery and cancer treatment.
Department of Urology, Tulane University School of Medicine, New Orleans, Louisiana 70112.
Caleb
C
Abshire
Department of Biomedical Engineering, School of Science and Engineering, Tulane University, New Orleans, Louisiana 70118; Tulane Institute for Integrative Engineering for Health and Medicine, Tulane University, New Orleans, Louisiana 70112.
Hakm Y
HY
Murad
Department of Chemical and Bimolecular Engineering, School of Science and Engineering, Tulane University, New Orleans, Louisiana 70118; Vector-Borne Infectious Disease Research Center, Tulane University, New Orleans, Louisiana 70112.
Jaspreet S
JS
Arora
Department of Urology, Tulane University School of Medicine, New Orleans, Louisiana 70112.
James
J
Liu
Department of Urology, Tulane University School of Medicine, New Orleans, Louisiana 70112.
Sree Harsha
SH
Mandava
Department of Chemical and Bimolecular Engineering, School of Science and Engineering, Tulane University, New Orleans, Louisiana 70118; Vector-Borne Infectious Disease Research Center, Tulane University, New Orleans, Louisiana 70112.
Vijay T
VT
John
Department of Biomedical Engineering, School of Science and Engineering, Tulane University, New Orleans, Louisiana 70118; Tulane Institute for Integrative Engineering for Health and Medicine, Tulane University, New Orleans, Louisiana 70112; Division of Urology, University of Arizona College of Medicine, Tucson, Arizona 85724.
Damir B
DB
Khismatullin
Department of Urology, Tulane University School of Medicine, New Orleans, Louisiana 70112; Division of Urology, University of Arizona College of Medicine, Tucson, Arizona 85724. Electronic address: brlee@tulane.edu.
Benjamin R
BR
Lee
D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D065546:Drug Liberation; D006358:Hot Temperature; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D008081:Liposomes; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000378:metabolism* / Q000528:radiation effects; D016896:Treatment Outcome; D000069453:Ultrasonic Waves
D008081:Liposomes; D047428:Protein Kinase Inhibitors
focused ultrasound; nanoparticles; renal cell carcinoma; thermally triggered chemotherapy; tyrosine kinase inhibitor