A Lighter Approach to Cancer Treatment

Although radiotherapy and chemo- therapy are powerful tools to treat cancer, they also cause major side effects by damaging or killing healthy cells as well as cancerous ones. At Kuwait University, Saad Makhseed is working on a technique that promises to kill cancer cells while leaving their healthy neighbors unharmed.
The approach, known as photodynamic therapy (PDT), relies on a combination of three ingredients — oxygen, light, and a type of molecule known as a photosensitizer — which are harmless individually but can kill a cell when brought together in the right way.
When a photosensitizer is illuminated by the correct wavelength, it reacts with nearby oxygen to transform it into a more reactive form known as singlet oxygen. These highly reactive oxygen molecules are toxic to cells, damaging their components and eventually causing them to die. By ensuring that the photosensitizer is only taken up by cancer cells and illuminating them as precisely as possible, clinicians can provide PDT to treat cancer without damaging any healthy tissue.
Makhseed, a chemist, had been studying molecules known as phthalocyanines (Pcs) in an effort to improve their performance as catalysts. While reading about these molecules, he discovered that they were being used in PDT. “I like medicine, so I started to read more about this line of research, the difficulties and challenges and what kinds of properties are needed to use these molecules for photodynamic therapy,” he said.

Refining Pcs for target treatment
In principle, Pcs are quite efficient at producing singlet oxygen, but a few drawbacks limited their use in practice. The first challenge is that Pc molecules aren’t soluble in water and so tend to clump together, forming aggregates that no longer react with oxygen.
To overcome this, Makhseed designed and synthesized Pcs with bulky attachments above and below them, like two donuts sandwiching the Pc core. By using charged attachments, he hoped to prevent the molecule from aggregating.
Makhseed reached out to Petr Zimcík of Charles University in the Czech Republic to help analyze the new molecules. “We had some facilities which Saad didn’t have at the time, so we were able to evaluate the compounds’ photo-physical properties,” said Zimcík. “The modifications perfectly inhibited aggregation, which is really important in this field. We really liked these molecules,” Zimcík added.
In continuing collaboration with Zimcík, Makhseed has refined the Pc design even further. The latest iteration replaces the zinc at the core of Pcs with indium, making them even more efficient at producing singlet oxygen.
The second major challenge is to ensure that Pcs are only taken up by cancer cells. This is accomplished by attaching specific functional groups to the Pcs to make them more attractive to cancer cells. For example, because cancer cells divide rapidly, they have higher metabolic rates than normal cells, so affixing a Pc to a sugar molecule would make it more likely to be taken up by a cancer cell.
Synthesizing large, complex molecules is no easy task. Thanks to funding from KFAS, Makhseed now has the facilities to test the photo- physical properties of the molecules he develops, but he still needs to send them to Zimcík and other collaborators for testing in cell cultures, and, eventually, in animal models.
Makhseed recently overcame the challenge of developing repeated synthesis techniques. “We developed a building block with certain functionality which lets us attach anything that we want to the phthalocyanine,” he said. Using this technique, he can generate Pcs with various attachments – carbohydrates, amino acids or lipids, for example – to target cancer cells. “By using existing information from biological research, we should be able to design molecules which are highly selective for cancer cells,” Makhseed said.
Makhseed has patented these molecules and the new synthesis technique, and he has high hopes for them. “These techniques will benefit not only Kuwaiti society, but the Gulf area and even the entire world,” he said. “This kind of treatment doesn’t involve a big procedure, so it can be done as often as needed. It can be highly selective, so there are no side effects for the patients, and there’s no need for an operation either.”
Zimcík is planning to include Makhseed’s molecules in a global project to test the efficacy of different Pcs. Along with Makhseed’s compounds, he is collecting molecules from labs in China, Russia, Spain, Poland, and elsewhere. “The biological assessment of PDT activity is done differently in every lab, which makes it problematic to compare the results,” Makhseed said. “So, we wanted to standardize the protocol and collect the best molecules that have been published and compare them to see what the differences are.”
Makhseed’s new technique for tweaking the structure of phthalocyanines also opens up the possibility of customizing them for use as catalysts, bringing him full circle. In addition to the PDT work, he’s developing Pcs customized to absorb carbon dioxide or purify water and is also starting a collaboration with a lab at Durham University in the UK to develop organic light-emitting diodes.
“For Kuwait, the knowledge we’re gaining is very important,” Makhseed said. “This research gives us novel information and helps us develop optimal molecules more quickly. I’m also building external collaborations and bringing that knowledge back to Kuwait.”
Makhseed hopes to see his work developed into an effective cancer treatment and become available to the public. “What we have now could be used as a medicine in the future if funders help us find the right people and set up clinical trials,” he said. “I want to be part of a field where we help people get treated, and even cured permanently.”