Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Opening a Door into Cells: Research Shows How Ultrasound Can Deliver Therapeutic Molecules into Living Cells

06.09.2006
Researchers have shown how ultrasound energy can briefly “open a door” in the protective outer membranes of living cells to allow entry of drugs and other therapeutic molecules – and how the cells themselves can then quickly close the door. Understanding this mechanism could advance the use of ultrasound for delivering gene therapies, targeting chemotherapy and administering large-molecule drugs that cannot readily move through cell membranes.

Using five different microscopy techniques, the researchers showed that the violent collapse of bubbles – an effect caused by the ultrasound – creates enough force to open holes in the membranes of cells suspended in a liquid medium. The holes, which are closed by the cells in a matter of minutes, allow entry of therapeutic molecules as large as 50 nanometers in diameter – larger than most proteins and similar in size to the DNA used for gene therapy.

“The holes are made by mechanical interaction with the collapsing bubbles,” said Mark Prausnitz, an associate professor in the School of Chemical and Biomolecular Engineering at the Georgia Institute of Technology. “The bubbles oscillate in the ultrasound field and collapse, causing a shock wave to be released. Fluid movement associated with the resulting shock wave opens holes in the cell membranes, which allow molecules from the outside to enter. The cells then respond to the creation of the holes by mobilizing intracellular vesicles to patch the holes within minutes.”

Done by scientists at Georgia Tech and Emory University in Atlanta, the research was reported in the journal Ultrasound in Medicine and Biology (Vol. 32, No. 6). The work was supported by the National Institutes of Health (NIH) and the National Science Foundation (NSF).

Ultrasound is the same type of energy already widely used for diagnostic imaging. Drug delivery employs higher power levels and different frequencies, and bubbles may be introduced to enhance the effect.

Ultrasound drug delivery could be particularly attractive for gene therapy, which has successfully used viruses to insert genetic material into cells – but with side effects. It could also be used for more targeted delivery of chemotherapy agents.

“One of the great benefits of ultrasound is that it is noninvasive,” Prausnitz said. “You could give a chemotherapeutic drug locally or throughout the body, then focus the ultrasound only on areas where tumors exist. That would increase the cell permeability and drug uptake only in the targeted cells and avoid affecting healthy cells elsewhere.”

Researchers have only recently found that the application of ultrasound can help move drugs into cells by increasing the permeability of cell membranes. It had been hypothesized, but not definitively shown, that the ultrasound increased the permeability by opening holes in cell membranes.

Prausnitz and collaborators Robyn Schlicher, Harish Radhakrisha, Timothy Tolentino, Vladimir Zarnitsyn of Georgia Tech and Robert Apkarian (now deceased) of Emory University set out to study the phenomenon in detail using a line of prostate cancer cells. They used scanning and transmission electron microscopy of fixed cells and two types of optical microscopy of living cells to assess ultrasound effects and cell responses.

Beyond demonstrating that ultrasound punched holes in cell membranes, the researchers also studied the mechanism by which cells repair the holes. After the ultrasound exposure, they introduced into the cell medium a chemical not normally taken up by the cells. By varying when the chemical was introduced, they were able to determine that most of the cells had repaired their membranes within minutes.

Though the researchers used prostate cancer cells in the study reported in the journal, they have also studied other types of cells and believe ultrasound offers a general way to briefly create openings in many classes of cells.

Researchers face a number of challenges, including FDA approval, before ultrasound can be used to deliver drugs in humans. For example, the effects of the ultrasound were not consistent across the entire volume of cells, with only about a third affected. Researchers will also have to address safety concerns and optimize the creation of collapsing bubbles – a phenomenon known as cavitation – within bodily tissues.

“Before we can use ultrasound for therapy in the body, we will have to learn how to control the exposure,” Prausnitz noted. “If we can properly design the impact that ultrasound makes on a cell, we can generate an impact that the cell can deal with. We want just enough impact to allow transport into the cell, but not so much of an impact that the cell would be stressed beyond its ability to repair the injury.”

Researchers don’t yet know if the membrane holes cause long-term harm to the affected cells. General assays show that cells survive after resealing the membrane holes, but detailed studies of cell behavior are still needed. Evidence from other researchers suggests that cell membranes are frequently damaged and repaired inside the body – without long-term ill effects. That suggests cells may similarly tolerate ultrasound’s effects.

“One of the real challenges is going to be translating the successes that have occurred in the laboratory and in small animals into clinical success in people,” said Prausnitz. “Now that we better understand the mechanism of ultrasound’s effects, we can more effectively take advantage of it for medical therapy.”

John Toon | EurekAlert!
Further information:
http://www.gatech.edu
http://www.gtresearchnews.gatech.edu/newsrelease/ultrasound.htm

More articles from Health and Medicine:

nachricht Investigators may unlock mystery of how staph cells dodge the body's immune system
22.09.2017 | Cedars-Sinai Medical Center

nachricht Monitoring the heart's mitochondria to predict cardiac arrest?
21.09.2017 | Boston Children's Hospital

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

Hope to discover sure signs of life on Mars? New research says look for the element vanadium

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>