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

Abstract:

: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.

journal_name

J Pharm Sci

authors

Abshire C,Murad HY,Arora JS,Liu J,Mandava SH,John VT,Khismatullin DB,Lee BR

doi

10.1016/j.xphs.2017.01.027

subject

Has Abstract

pub_date

2017-05-01 00:00:00

pages

1355-1362

issue

5

eissn

0022-3549

issn

1520-6017

pii

S0022-3549(17)30061-8

journal_volume

106

pub_type

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