Are parasites reliable as drug "couriers"? | Ficus microcarpa

Hello, I am Rong Ge from the China Science and Technology Museum. Welcome to Rong Ge's Science. The brain, as the highest achievement in the process of biological evolution, is also the organ we are most curious about and least understood.

The human body is a complex and huge system. Each of its components: organs, tissues and cells cannot survive independently. They must be constantly supplied with oxygen and nutrients, and constantly carry away metabolic waste and toxins. This work mainly relies on the blood circulation system throughout the body. It should be noted that the length of all human blood vessels added together exceeds 100,000 kilometers. Those capillaries throughout the body reach and serve every corner except hair, teeth, and cornea. As a core component that accounts for only 2% of the body's weight but consumes 25% of oxygen, the brain is of course inseparable from the support of capillaries. Once the blood supply to the brain is stopped, it only takes two minutes for brain cells to stop functioning due to lack of oxygen, and five minutes will cause irreversible damage to brain tissue.

On the other hand, as the most sophisticated organ in the human body, the brain requires an extremely stable chemical environment. After all, we need various neurotransmitters to trigger various reactions and weave them into complex inputs and outputs. It is necessary to strictly control what substances the brain can come into contact with, and to isolate potentially pathogenic microorganisms from the brain. The blood-brain barrier is what accomplishes this arduous mission.

In fact, the structure of general peripheral capillaries is relatively loose, with gaps everywhere on the blood vessel walls, allowing substances inside and outside the blood vessels to enter and exit freely and exchange, which is also the basis for blood vessels to supply nutrients and collect waste. But in the brain, capillaries are divided into several layers from the inside to the outside:

First, tight junctions are formed between the endothelial cells that make up the blood vessel wall.

Then there is a thin and flexible basement membrane surrounding the blood vessel wall;

Finally, outside the basement membrane, the glial cells in the brain will add another layer of wrapping. This three-layer structure effectively prevents the leakage of substances in the blood vessels. Only a very small number of substances, such as oxygen molecules and fat molecules, can passively diffuse and freely pass through this membrane. And important nutrients such as glucose and amino acids must also pass through the special "checkpoint" proteins on this membrane to be identified and actively transported to the brain. Just like most community express deliveries can be delivered directly to the door, the brain community has community "security guards" and only those who register can pass.

The role of this "security guard" is very important. Once it is damaged, it may lead to various diseases. For example, multiple sclerosis is a common neurological disease. The blood-brain barrier is damaged, and immune cells enter the brain with blood circulation, attacking special substances on the surface of brain neurons, affecting the patient's sensory, motor, mental and other abilities. But on the other hand, it is this barrier that has created a huge obstacle for people to develop drugs for brain diseases. In order to allow biomacromolecule drugs, such as protein drugs, antibody drugs, cell gene therapy drugs, etc. to cross the blood-brain barrier, drug developers have tried their best. For example, some people have thought of using parasites that can enter the brain to deliver drugs, which is a real brain-opening idea.

Toxoplasma gondii should be familiar to cat owners. It is a tiny intracellular parasite. The only known final host is the cat, and it can only reproduce sexually in the cat's body. At the same time, Toxoplasma gondii can survive in a variety of vertebrates, including humans, causing certain damage to them. Even pregnant women infected with Toxoplasma gondii may cause fetal malformation or even death. The most amazing and noteworthy thing about Toxoplasma gondii is that after infecting an animal, it can enter its brain, parasitize in nerve cells, and change the animal's behavior. When it parasitizes in the brain of a mouse, it can change the mouse from being afraid of cats to being willing to approach cats! This makes it easier for the cat to eat it, thereby helping Toxoplasma gondii survive and complete reproduction.

At present, relevant experiments have achieved preliminary results, but there is still a long way to go before the successful, safe and effective delivery of drugs. But no matter what, using the crossing mechanism formed by long-term survival pressure to penetrate the blood-brain barrier formed by long-term evolution can be regarded as defeating magic with magic.