Thursday, December 08, 2022

How to activate drugs with light to treat diseases

Have you ever wondered what happens when we take a medicine like ibuprofen? After swallowing, the medicine moves down the throat and Magical It can relieve a headache, relieve back pain, or reduce swelling from a sprained ankle. But how does the medicine get where it should work?

In fact, most drugs are not selective, but are distributed throughout the body. When ibuprofen reaches the bloodstream, it travels through the circulatory system until it finds the area causing the pain. There it binds to its target molecules, which are involved in the release of substances responsible for pain and inflammation. When attached, it blocks its action and reduces its effects.

However, these target molecules also participate in the production of compounds that protect the gastric mucosa. Ibuprofen also inhibits them, causing the stomach wall to weaken.

This is a typical case of side effect. It’s not just about ibuprofen. Most drugs are designed to produce a desired effect at a particular location. But given its non-specific accumulation in the body and the presence of target molecules in other parts of the body, all the drugs we take have side effects.

A new approach to solve this problem has aroused the interest of the scientific community. This is phytopharmacology, an emerging discipline that aims to develop “photosensitive” drugs or “phytopharmaceuticals”.

remote control medicine

Phytopharmaceuticals are chemical compounds capable of capturing light energy. These compounds generally do not have therapeutic activity. So how do they work?

When a beam of light hits them, they get activated and trigger a series of biological reactions. In theory, this would be a tremendous advantage as we can control where, when and how strongly we want a particular effect.

The use of light makes it possible to control pharmacological action in time and space, as if it were a switch: only where it is applied do these reactions occur. This will reduce the side effects on the rest of the body.

Captive Drugs, Photointerruptors and Photosensitizers

There are three main modalities within photopharmacology.

The first one is based on the use of “cage drugs” (photocages, These are chemical compounds that, like a cage, surround the active principle of a given drug. When irradiated with light, the drug is released and regains its activity (Figure 1A).

The photopharmaceutical JF-NP-26, recently developed by a team of scientists from the University of Barcelona, ​​is one example. The drug’s fluorescence leads to breakdown that releases resglurant, a painkiller that was rejected in clinical trials for causing liver toxicity. Using pulses of blue light, researchers were able to control pain in lab rats without observing side effects in the liver.

The second method uses “photointerrupters” (photo switch, These are designed so that they undergo changes in their spatial structure when illuminated (Figure 1B). The new structure allows the photoswitch to bind to its target and produce a pharmacological effect.

An example of them are azobenzenes, which have a linear orientation in space, but adopt a curved geometry due to the influence of light. In 2012, scientists from the University of Berkeley (USA) managed to restore sight to blind rats using azobenzene-type photoswitches. In their study, they administered photopharmaceuticals to animals with rhinitis pigmentosa, a pathology that causes retinal degeneration. These azobenzenes bind to ion channels found in retinal neurons. By applying ultraviolet light, the change from linear to curved unblocks the channels, restoring the nerve impulse and, with it, the vision of the blinded animals.

The third method is “photodynamic therapy”. Unlike the previous ones, this technique has been successfully used in hospitals since the 1970s, mainly to combat cancer. The mechanism is also different from the previous ones, because in addition to the drug and light, a third element is involved, oxygen, which is present inside our cells (Figure 1C).

In this case, “photosensitizing drugs” are used (photosensitizers, Its job is to transfer light energy into cellular oxygen. This energy transfer activates the oxygen molecules and converts them into reactive oxygen, which is highly toxic to cells. In this way, only where the light is applied – in the area of ​​the tumor – will this reactive oxygen be generated to induce cell death. In this therapy, the most commonly used drugs are porphyrins, whose clinical efficacy has been demonstrated in some types of skin cancer.

bright future

Although promising, photopharmacology faces several challenges in reaching the clinic.

  1. Get the light to reach the internal tissues of the body.
  2. Toxicity of the photopharmaceuticals themselves or their metabolic inactivation before reaching the target.
  3. In the case of photodynamic therapy – more advanced in clinical use – sensitivity to sunlight is one of the major drawbacks.

However, scientific and technological advances are managing to solve these problems, either with infrared light probes—which have greater penetration—developing molecules with better effectors or by refining photoactivation mechanisms.

From cancer to blindness, photopharmacology opens the door to treating disease while minimizing side effects. Optical control of biological processes has ceased to be a pipe dream to become a viable reality in laboratories.

These strategies have yet to make the leap toward an integrative medical application. But we’re getting closer to seeing how this science illuminates the drugs of the future.

This article was originally published on The Conversation. read the original.

Enrique Ortega Forte is not paid a salary, nor does he do consulting work, nor does he own shares in, nor does he receive funding from, any company or organization that could benefit from this article, and he has declared That he/she has no relevant affiliation beyond the above mentioned academic position.

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