Sonoporation generates downstream cellular impact after membrane resealing
Xinxing Duan1,2, Qian Zhou2, Jennifer M F Wan3
1Schlegel Research Institute for Aging & Department of Electrical and Computer Engineering, University of Waterloo, Waterloo, ON, Canada.
Scientific Reports
|March 5, 2021
Summary
Ultrasound sonoporation can deliver drugs but may cause delayed cell death. Even if cells survive membrane repair, they can still undergo apoptosis or necrosis, highlighting the need for refined therapeutic protocols.
Area of Science:
- Biomedical Engineering
- Cell Biology
- Acoustic Medicine
Background:
- Sonoporation uses ultrasound and microbubbles for enhanced drug and gene delivery.
- Limited understanding of post-resealing cellular effects hinders efficient sonoporation application.
- Investigating downstream cellular impacts after membrane resealing is crucial.
Purpose of the Study:
- To elucidate the mechanistic details of sonoporation-induced cellular hemostasis disruption.
- To differentiate sonoporation's effects from general ultrasound exposure on cells.
- To assess cell viability, proliferation, cell cycle, and gene expression post-sonoporation.
Main Methods:
- Sonoporation applied to HL-60 leukemia cells using pulsed ultrasound and lipid-shelled microbubbles.
- Specific ultrasound parameters: 1 MHz frequency, 0.50 MPa peak negative pressure, 10% duty cycle, 30s exposure, 29.1 J/cm² energy density.
- Cell viability, apoptosis/necrosis, proliferation, cell cycle, and HSP-70 gene expression analyzed at various time points (3h, 12h, 24h).
Main Results:
- 54.6% of initially viable sonoporated cells underwent apoptosis or necrosis by 24h.
- Sonoporated cells exhibited reduced proliferation by 43.8% over 24h.
- Cell cycle distribution altered by 12h, and heat shock protein-70 (HSP-70) gene expression upregulated by 4.1-fold at 3h post-exposure.
Conclusions:
- Sonoporation triggers cellular attempts to restore homeostasis post-membrane resealing.
- Many sonoporated cells ultimately fail to recover, leading to delayed cell death.
- Mechanistic insights gained can inform the development of improved sonoporation-based therapies.
