Abstract
The aim of our study was to evaluate the influence of low-intensity pulsed US on the delivery of doxorubicin (DOX) into MDA-MB-231 triple-negative breast cancer and A549 non-small cell lung cancer cell 2D and 3D cultures. US with pulse repetition frequency of 10 Hz and 1 MHz center frequency was generated with peak negative pressure of 0.5 MPa and 50% duty cycle. SonoVue microbubbles were used. Spheroids were formed using 3D Bioprinting method. DOX delivery in 2D and 3D cultures was assessed using fluorescence microscopy. US without the addition of microbubbles did not enhance the penetration of DOX into monolayer-cultured cells and tumor spheroids. In the presence of microbubbles US improved the delivery of DOX into the edge end middle zones of A549 and MDA-MB-231 spheroids. Application of low-intensity pulsed US in combination with microbubbles may be a promising approach to enhance the delivery of DOX into tumor spheroids.
Highlights
The aim of our study was to evaluate the influence of low-intensity pulsed US on the delivery of doxorubicin (DOX) into MDA-Microbubbles SonoVue (MB)-231 triple-negative breast cancer and A549 non-small cell lung cancer cell 2D and 3D cultures
The aim of our study was to evaluate the influence of microbubble-assisted low-intensity pulsed US on the delivery of doxorubicin (DOX) into monolayer-cultured A549 non-small cell lung cancer and MDA-MB-231 triple-negative breast cancer cells (2D cultures) and tumor spheroids (3D cultures). 3D cultures of cells is a spatially arranged group of cells and they are not limited by a single plane only, mimicking the real spatial arrangements of cells within a tissue of the real tumour
Escoffre et al.[21] showed that the combination of US and Vevo MicroMarker microbubbles slightly enhanced DOX uptake into monolayer cultured MDA-MB-231 cells and increased DOX-induced cell death, SonoVue microbubbles did not enhance the effect of DOX on these cells
Summary
The aim of our study was to evaluate the influence of low-intensity pulsed US on the delivery of doxorubicin (DOX) into MDA-MB-231 triple-negative breast cancer and A549 non-small cell lung cancer cell 2D and 3D cultures. Application of low-intensity pulsed US in combination with microbubbles may be a promising approach to enhance the delivery of DOX into tumor spheroids. Poor drug delivery into cancer cells is one of the biggest concerns in anticancer therapy It is the result of various factors such as poor tumor vascularization, hypoxia, or increased interstitial fluid pressure in tumors[1,2]. When the intensity of US increases and the acoustic pressure exceeds a certain threshold, the changes of the microbubble volume start being controlled by the inertia of the surrounding liquid[8] This type of cavitation is called inertial cavitation. The collapse of microbubbles may cause the formation of microjets that can form pores in the cell membrane[10] Through those ruptures, drugs penetrate into cells via passive diffusion.
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