Transport vehicles for medicines reach their destination faster

MWith a good 200,000 new cases every year, skin cancer is one of the most common types of cancer in Germany. Anyone who recognizes it early usually gets off lightly – thanks in part to modern methods such as photodynamic therapy, or PDT for short. In PDT, affected skin areas are treated without damaging the surrounding healthy skin. At the beginning of the treatment, the diseased area is treated with a special ointment that contains a light-sensitive porphyrin ingredient.

After an exposure time of two to three hours, the affected area is irradiated with a strong light source, whereupon the active substance kills tumorous tissue in a targeted manner. The skin usually recovers a few days after the procedure. As with any cancer, follow-up examinations and, if necessary, follow-up treatments should be carried out. The chances of success of PDT are good – the risks are low. Severe cases of acne or certain eye diseases can also be treated with photodynamic therapy.

The procedure is minimally invasive and targeted. But how does the drug know when and where to release its cytotoxic effect? The answer lies in the packaging: the porphyrin contained in the ointment is embedded in so-called liposomes, which serve as the active ingredient transport system. Liposomes are nanometer-sized bubbles made of a lipid bilayer and are among the lipid nanoparticles that are also used, among other things, as a transport system for mRNA vaccines.

PDT takes advantage of the fact that certain macromolecules, such as liposomes, increasingly accumulate in tumor tissue. This increases the likelihood that the tumor cells will take up the nanoparticles. In this way, the drug gets to exactly where it is supposed to work later.

Accelerated absorption of the liposomes

Inside the liposomes, the toxic porphyrins are in a deactivated state. The porphyrin active ingredient used is structurally closely related to natural dyes such as chlorophyll or hemoglobin – and is harmless per se. It only becomes effective when the liposome is broken down in the tumor cell and then targeted external radiation is carried out as part of PDT. Under these circumstances, porphyrins locally release reactive oxygen species that ultimately induce cell death of the cancer cell. The actually toxic species is therefore only generated within the tumor cells during irradiation – healthy cells are spared.

In addition, the porphyrin-loaded liposomes can also be used as a contrast agent specifically for tumor cells. Because only the free, i.e. digested, porphyrins are fluorescent, which means that they specifically mark tumor cells under the fluorescence microscope.

The bottleneck of such nanomedical procedures is often the absorption rate of the nanoparticles by the tumor cells. This is where a discovery by a research group headed by Gang Zheng from Toronto comes in: Thanks to a small modification of the liposomes, the active ingredient is absorbed 25 times faster.

They succeeded in doing this by incorporating EDTA molecules into the liposomes, the scientists report in the journal Angewandte Chemie. EDTA is known as a drug against heavy metal poisoning or as an additive to detergents to prevent calcification of washing machines. According to the researchers working with Zheng, EDTA acts as a surfactant on the cell membrane of the tumor cell, making it more liquid and therefore more receptive to the nanoparticles.

As a control, the scientists tested photodynamic therapies with and without EDTA-containing liposomes on living mice with tumors. Four weeks after treatment, all mice remained alive on the optimized therapy; with conventional therapy, at least 60 percent survived. In tests on human cell cultures, the EDTA-tipped lipid nanoparticles killed over 95 percent of the tumor cells after just 24 hours. Zheng and his colleagues hope that their research results will increase the chances of success for future nanomedical therapies.

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