Immunotherapies are increasingly used in the fight against cancer and aim to stimulate the immune system to defend itself by destroying tumor cells. Although these treatments are often effective, their significant impact on the body can generate serious side effects. To increase their accuracy and limit unwanted side effects, a team from the University of Geneva (UNIGE) and Ludwig-Maximilian University in Munich (LMU) have developed silicon dioxide nanoparticles with a very precise opening mechanism that can transport the drug exactly to where it should act. These microscopic carriers can be used not only to treat cancer, but also to deliver other drugs to the very heart of our immune system, thus paving the way for completely new therapeutic or preventive strategies. These results can be read in the journal ACS Nano.
In medicine, nanoparticles are used to encapsulate a drug to protect it: indeed, their nano size allows dendritic cells to accept them, the body’s first line of defense. “The function of dendritic cells is to phagocytose foreign elements to bring them to the lymph nodes and thus trigger an immune response,” explains Carole Bourquin, a professor at UNIGE School of Medicine and Science who led this research. “We use this mechanism to have these cells transport the drug encapsulated into nanoparticles, which thus directly reaches the lymph nodes, where the immune response is triggered.”
Silica, a material with multiple properties
Although nanoparticles are already used in certain treatments – the latest example is the messenger RNA vaccine against Covid-19 – the system can still be improved. “Medical nanoparticles are mostly composed of polymers or lipids,” says Julia Wagner, a doctoral student in Professor Bourquin’s lab and the first author of this work. “However, in some cases the solubility of the substance being transported is not compatible with the characteristics of the nanoparticles. This prevents the particles from filling with the drug. “
Scientists have therefore turned to silicon dioxide, a mineral that can be found naturally in the environment. “Silicon nanoparticles are like small sponges with cavities that can be easily filled and whose properties can be adjusted to better match the properties of the drug,” explains Julia Wagner. “The antitumor drug we used, for example, has already been tested with other particles, but it often leaked out too quickly.”
A lid that opens only in the right place
To further improve the performance of their particles, the research team added a lid that covers the drug-filled cavities and prevents the drug from escaping during transport. “The lid reacts according to the pH of the environment: when the particles circulate in the blood, which has a neutral pH around 7.40, it stays firmly in place. But after the dendritic cells take over the particles, they reach the vesicles inside the cell whose pH is acidic. Then the lid is removed and the medicine is released, ”reports Carole Bourquin.
This technical ability ensures high precision of treatment: the seal maintains the integrity of the drug, and thus the duration of action, while preventing its spread in the body, thus reducing unwanted side effects. Indeed, some drugs stimulate the immune system extremely strongly, but disappear within a few hours, requiring repeated administration of high doses. “With our nanoparticles, the drug can work six times longer, which would allow for lower and better tolerated doses,” the authors say. Their work provides evidence of the concept of the mechanism that governs these nanoparticles, which can be used against cancer as well as against other diseases, or as part of preventive or therapeutic vaccines. “Our work will now continue to confirm these initial results and reproduce their validity with a wider range of antitumor drugs.”
Reference: Wagner J, Gößl D, Ustyanovska N, et al. Mesoporous silica nanoparticles as a pH-responsive carrier for a drug that activates immune resiquimod enhance the local immune response in mice. ACS Nano. 2021; 15 (3): 4450-4466. doi: 10.1021 / acsnano.0c08384
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