Hokkaido University Research Profiles

Life Sciences

Sonoporation: Development of a New Drug Delivery Method Using Ultrasound and Microbubbles

Realization of tissue targeting capability at the cellular level

We were the first in the world to show that, by irradiating cells with pulsed ultrasound while microbubbles of several microns in diameter are attached to the cells, we can temporarily increase the cell membrane permeability. We are now promoting research aimed at realizing drug and gene delivery to living organisms.

Content of research

○ Acoustic perforation (sonoporation) using microbubbles and pulsed ultrasound: Pulsed ultrasound irradiation of microbubbles in contact with the cell membrane enables temporary perforation only at the attachment site (Fig. 1). We have realized a method to deliver drugs or genes into any desired position in the target cell by adding drugs or genes to the microbubbles and controlling the attachment site with optical tweezers.
○ Succeeding with therapeutic site identification and drug delivery by using microbubbles and an ultrasound system: A microbubble, which has the target function of adhering only to the cells to be treated, is injected into a vein. To identify the therapeutic site, the tissue where the bubbles have accumulated is detected using an ultrasound contrast method. Pulsed ultrasound waves are then generated to break the bubbles, allowing temporary perforation of the cell membrane and drug delivery (Fig. 2). By adding drugs or genes to the bubbles, highly efficient drug delivery only to the target cells can be realized.

  • Before ultrasound irradiation
    Fig. 1

  • After irradiation
    Fig. 2

Potential for social implementation

  • ・Electroporation alternative
  • ・DDS (Drug Delivery System)
  • ・Early diagnosis of cancer
  • ・Enhanced efficacy of anticancer drug therapy
  • ・Immunotherapy
  • ・Gene transfer

Appealing points to industry and local governments

・Replacement technology for electroporation
We have succeeded in selectively delivering drugs and genes to desired cells by controlling the size of the bubbles, their attachment position to cells and the conditions of ultrasound irradiation.
・We have realized both ultrasound diagnosis and treatment, and have also succeeded with in vivo drug and gene delivery with high safety. Currently, we are working to develop a method to deliver immune substances into dendritic cells to promote immunotherapy.