By applying ultrasound to air bubbles (microbubbles) that are a few microns smaller than red blood cells,
DDS (drug delivery system) delivers drugs to targeted cells and tissues.
It is expected that the results of this research will be useful in treating cancer and brain and central nervous system diseases.
Professor Ryo Suzuki, who is researching microbubbles,
We are trying to open up new possibilities by endowing these tiny bubbles with various functions.

With microbubbles and ultrasound
Deliver the drug to the target

Blood-brain barrier opening technology

When ultrasonic waves are applied to the microbubbles in the blood, the microbubbles contract and expand (vibration). In addition, the microbubbles collapse as the ultrasonic energy is gradually increased. When the mechanical action due to the vibration or crushing of such microbubbles is induced in the blood vessel, the blood vessel wall in the area irradiated with ultrasonic waves is expanded, and a small gap is opened in the blood vessel. As a result, the drug flowing in the blood vessel leaks to cells and tissues outside the blood vessel. This mechanism is the DDS that delivers medicines to the necessary cells and tissues in a pinpoint manner.

Not only delivering medicines to cancer cells
Also has the effect of activating immune cells

Microbubbles developed for medical use consist of hydrophobic gases covered in an outer shell made of lipids or other materials. This is fine when used as a blood flow contrast agent, but for use in DDS, they have the disadvantage of being unstable in the blood and disappearing within a few minutes. Professor Suzuki and his colleagues, who have been considering using them in DDS, which requires even higher functionality, have focused on the components of the microbubble outer shell. They have succeeded in giving the bubbles functions tailored to their purpose, such as modifying the bubble surface with target molecules that tend to gather in specific locations.

One of the targets is cancer tissue. Cancer tissue is characterized by having more new blood vessels than normal tissue, but even among normal tissues, it is rich in blood vessels and easily affects hair roots, intestinal tract, bone marrow, etc., which are prone to growth, such as hair loss, vomiting / diarrhea, and cytopenia. It will cause side effects. In addition, for pancreatic cancer, which has a small blood vessel volume and is difficult to deliver drugs, and breast cancer, which has a large blood vessel volume but easily metastasizes to the brain and lungs, a large number of anticancer drugs can be pinpointed to the tumor. Must be delivered.

Professor Suzuki therefore administered anti-cancer drugs and microbubbles at the same time, and irradiated the target cancer tissue with ultrasound from outside the body. The microbubbles vibrated and collapsed, causing the anti-cancer drugs to leak into cells outside the blood vessels. Experiments using mice showed that the same effect could be achieved with one-fifth the usual dosage of the drug.
"Currently, we administer microbubbles and anticancer drugs simultaneously. Eventually, we hope to be able to load anticancer drugs onto microbubbles, or to modify the surface of microbubbles with molecules that actively attract cancer cells," says Professor Suzuki.

Dynamics control using ultrasonic waves of anticancer drugs

It has become clear that there are other effective ways to treat cancer besides drugs. When ultrasound is applied using only microbubbles without using drugs, cytotoxic T cells, which are involved in anti-tumor immunity, are activated and attack cancer cells.
"If we can activate the immune system against cancer cells, it will broaden the scope of treatment, allowing the immune system to attack metastatic cancer, which is difficult to treat with drugs," Professor Suzuki.

If it can penetrate the blood-brain barrier
Expanding the possibilities of dementia treatment

Increased vascular permeability with microbubbles and ultrasound may lead to the treatment of "brain disorders" that modern medicine cannot overcome. The number of people who develop various brain diseases with aging, such as dementia such as Alzheimer's disease and Parkinson's disease, brain tumors, and nerve cell damage due to cerebral infarction, has become a major social issue. To that end, the world has been working on the development of therapeutic and preventive drugs, and despite many reports that they have achieved sufficient results at the laboratory level, all drugs are effective at the stage of clinical trials. Not done.

The cause is the problem of the blood-brain barrier (BBB). At the blood-brain barrier, vascular endothelial cells in the brain are strongly bound to each other by "tight junctions", and foreign substances cannot easily enter the brain. Thanks to this, the important brain is protected, but the medicine in the blood cannot penetrate into the brain, so the medicine does not work.

Examination of Blood-Brain Barrier (BBB) Opening

In an experiment in which Professor Suzuki and his colleagues injected microbubbles and a drug into a mouse's tail and then irradiated it with ultrasound from above the skull, they confirmed that the drug penetrated the brain's capillaries and migrated into the brain.

"If we can overcome the major hurdle of the blood-brain barrier, we may be able to rediscover effective drugs from among the dementia treatments that have been deemed ineffective until now. Research teams overseas have reported results such as stimulating nerve cells in the brain and treating intractable brain tumors using a similar method, which is likely to greatly expand the possibilities for treating brain and central nervous system diseases," says Professor Suzuki.

To realize theranostics
Established a university-launched venture

Professor Suzuki and his colleagues, who have been conducting research and development on microbubbles, founded the university-based venture WellCera (represented by his predecessor, Professor Emeritus Kazuo Maruyama), with the aim of developing more effective functional microbubble formulations and manufacturing investigational drugs. Microbubbles can be used as ultrasound contrast agents and as therapeutic tools for DDS. In recent years, the word "theranostics" has been coined to describe such systems that can perform both diagnosis and treatment with a single tool. This word is a combination of "therapeutics" and "diagnostics," and it is the medical technology that Professor Suzuki and his colleagues are aiming for with microbubble DDS.

"In conventional cancer treatments, treatment plans are decided based on test results, and treatment begins several days later. On the other hand, with testing agents that also have therapeutic effects, such as microbubble formulations, testing and treatment can be performed simultaneously, minimizing the burden on patients while ensuring reliable treatment. Theranostics must be realized for the future advances in medicine," says Professor Suzuki.

To realize theranostics, collaboration with a wide range of research fields is essential, including not only microbubble technology, but also both hardware and software ultrasound technology, and disease-specific medical knowledge. "I find it thrilling to team up with experts from various fields both inside and outside the university and explore niche interdisciplinary areas," says Professor Suzuki.

DDS using microbubbles is showing results in the treatment of cancer and brain/central nervous system diseases, and there is potential for further treatments to be established depending on the functions that can be added in the future. Professor Suzuki is driven by his desire to "eliminate the pain of many patients with DDS and contribute to improving their Quality of Life (QOL)," and is challenging all possibilities.