Stimulating the immune system with sponges made of silica
Silica nanoparticles developed by a team from the UNIGE and Ludwig-Maximilian AV短视频 of Munich have significantly increased the effectiveness and precision of immunotherapies.
Confocal microscope image of immune cells (in red). In green, silica nanoparticles. The nanoparticles, once absorbed by the immune cells, appear in yellow.听漏 UNIGE, Carole Bourquin
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Immunotherapies are increasingly used to fight cancer and aim to stimulate the immune system to defend itself by destroying tumour cells. While these treatments are often effective, their significant impact on the body can generate severe side effects. In order to increase their precision and limit undesirable side effects, a team from the AV短视频 (UNIGE) and the Ludwig-Maximilian AV短视频 of Munich (LMU) has developed silica nanoparticles with a very precise opening mechanism that can transport a drug exactly to where it should act. These microscopic vehicles could possibly be used not just for cancer treatment, but also to deliver other drugs at the very heart of our immune system, thus paving the way for entirely new therapeutic or preventive strategies. These results can be read in the journal ACS Nano.
In medicine, nanoparticles are used to encapsulate a drug in order to protect it: indeed, their nanosize allows them to be taken up by dendritic cells, the body鈥檚 first line of defence. 鈥淭he function of dendritic cells is to phagocytose foreign elements to bring them to the lymph nodes and thus trigger the immune response鈥�, explains Carole Bourquin, professor at the UNIGE Faculties of Medicine and Science, who led this research. 鈥淲e are taking advantage of this mechanism to have these cells transport a drug encapsulated into nanoparticles, which thus reaches the lymph nodes directly, where the immune response is initiated.鈥� 听
Silica, a material with multiple properties
Although nanoparticles are already used in certain treatments 鈥� the most recent example being the messenger RNA vaccines against Covid-19 鈥� the system can still be improved. 鈥淢edical nanoparticles are generally composed of polymers or lipids鈥�, says Julia Wagner, a PhD student in Professor Bourquin鈥檚 laboratory and the first author of this work. 鈥淚n some cases, however, the solubility of the substance to be transported is incompatible with the characteristics of the nanoparticles. This makes it impossible to load the particles with the drug.鈥�
The scientists therefore turned to silica, a mineral that can be found naturally in the environment. 鈥淪ilica nanoparticles are like little sponges with cavities that can easily be filled and whose properties can be modified to better match those of the drug鈥�, explains Julia Wagner. 鈥淭he anti-tumour drug we used, for example, had already been tested with other particles, but it often leaked out too quickly.鈥�
A lid that only opens in the right place
To further improve the performance of their particles, the research team added a lid that covers the drug-laden cavities and prevents the drug from escaping during transport. 鈥淭he lid reacts according to the pH of its environment: when the particles are circulating in the blood, which has a neutralpH of around 7.40, it remains firmly in place. But once the particles are taken up by the dendritic cells, they arrive in vesicles inside the cell whose pH is acidic. Then the lid comes off and the drug is released鈥�, reports Carole Bourquin.
This technical prowess ensures the high precision of the treatment: the seal maintains the integrity of the drug, and therefore its duration of action, while preventing it from spreading in the body, thus reducing undesirable side effects. Indeed, some drugs stimulate the immune system extremely strongly, but disappear within a few hours, requiring repeated administration of high doses. 鈥淲ith our nanoparticles, the drug can take effect up to six times longer, which would make it possible to administer lower and better tolerated doses鈥�, say the authors. Their work provides a proof of concept of the mechanism governing these nanoparticles, which could be used against cancer as well as against other diseases, or as part of preventive or therapeutic vaccines. 鈥淥ur work will now continue in order to confirm these initial results, and to reproduce their validity with a wider range of anti-tumour drugs.鈥�