Optimization of ultrasound parameters for microbubble-nanoliposome complex-mediated delivery

Abstract

Purpose:The aim of this study was to identify the optimal ultrasound (US) parameters for gene and drug delivery.Methods:In order to target SkBr3, which is a breast cancer cell overexpressing the Her2 receptor, trastuzumab (Herceptin) was used. Micobubble-nanoliposome complex (MLC) was mixed with trastuzumab and stored overnight. Finally, MLC was combined with Her2Ab. A US device equipped with a 1-MHz probe was used for delivery to the cell. Several parameters, including intensity (w/cm2), time (minutes), and duty cycle (%), were varied within a range from 1 w/cm2, 1 minute, and 20% to 2 w/cm2, 2 minutes, and 60%, respectively. A confocal laser scanning microscope (CLSM) was used to confirm the delivery of MLC to the cells after US treatment.Results:MLC with fluorescent dyes and trastuzumab was synthesized successfully. By delivering MLC with Her2Ab to cells, the targeting effect of trastuzumab with MLC was confirmed by CLSM. The cell membranes showed green (fluorescein isothiocyanate) and red (Texas red) fluorescence but treatments with MLC without Her2Ab did not show any fluorescence. Optimal conditions for US-mediated delivery were 1 or 2 w/cm2, 2 minutes, and 60% (uptake ratio, 95.9% for 1 w/cm2 and 95.7% for 2 w/cm2) for hydrophobic materials and 2 w/cm2, 2 minutes, and 60% (uptake ratio, 95.0%) for hydrophilic materials.Conclusion:The greater the strength, duty cycle, and period of US application within the tested range, the more efficiently the fluorescent contents were conveyed.

Clinical study of ultrasound and microbubbles for enhancing chemotherapeutic sensitivity of malignant tumors in digestive system

“…Despite the many studies on ultrasound-mediated gene and drug delivery using microbubbles, the conditions under which ultrasound-mediated delivery is most effective have not been determined ( 50 - 52 ). Although this study identified a relatively good MI, the sample size was small for determining the ideal MI.…”

Nanoparticle-assisted ultrasound: A special focus on sonodynamic therapy against cancer

“…At the same time, the carrier shows a rapid release of the drug once inside the tumor, also limiting the healthy tissue exposure [70][71][72].…”

“…To reduce the detrimental side effects of toxic chemotherapeutic drugs, the ultimate strategy is to encapsulate the drugs in a vehicle (either an organic or inorganic micro or nano-sized carrier) showing a very low leak rate in circulation. At the same time, the carrier shows a rapid release of the drug once inside the tumor, also limiting the healthy tissue exposure [ 70 – 72 ].…”

Low‑frequency ultrasound and microbubbles combined with simvastatin promote the apoptosis of MCF‑7 cells by affecting the LATS1/YAP/RHAMM pathway

“…The biological influence of LFU and microbubbles on cancer cells is dependent on the microbubble density, ultrasound intensity and irradiation time ( 34 , 35 ). Generally, a pilot experiment should be prepared to debug the optimized ultrasound parameters, so as to induce cell apoptosis to the maximum extent ( 36 , 37 ). Studies have identified that microbubbles enhance ultrasound exposure by decreasing the cavitation threshold ( 27 ), which induces cancer cell apoptosis ( 38 , 39 ).…”