Focused Ultrasound–Triggered Release of Tyrosine Kinase Inhibitor From Thermosensitive Liposomes for Treatment of Renal Cell Carcinoma

Caleb Abshire, Hakm Y. Murad, Jaspreet S. Arora, James Liu, Sree Harsha Mandava, Vijay T. John, Damir B. Khismatullin, Benjamin R. Lee

Research output: Contribution to journalArticle

7 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1355-1362
Number of pages8
JournalJournal of pharmaceutical sciences
Issue number5
StatePublished - May 1 2017
Externally publishedYes



  • focused ultrasound
  • nanoparticles
  • renal cell carcinoma
  • thermally triggered chemotherapy
  • tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Pharmaceutical Science

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