This image shows macrophages (in green) interacting with nanoparticles. Image: Laboratoire Bourquin - UNIFR/UNIGE.The use of nanoparticles is becoming increasingly widespread in the world of biomedicine. This rapidly-evolving technology offers hope for many medical applications, whether for diagnosis or therapies. In oncology, for example, a growing body of research suggests that, thanks to nanoparticles, treatment will soon become more precise, more effective and less painful for patients.
One potential stumbling block, however, is that the way nanoparticles interact with the immune system has remained unclear and unpredictable, restricting their potential medical use. Now, researchers from the universities of Geneva (UNIGE) and Fribourg (UNIFR), both in Switzerland, are close to solving the problem.
They have devised a rapid screening method for selecting the most promising nanoparticles, thereby fast-tracking the development of future treatments. In less than a week, they can determine whether or not nanoparticles are compatible with the human body – an analysis that previously required several months of work. This discovery, which is described in a paper in Nanoscale, may well lead to the swift, safe and less expensive development of nanoparticles for medical applications.
Nanoparticles measure between 1nm and 100nm in size, approximately the size of a virus. Their very minuteness means that they have the potential to be used in a wide range of medical applications, such as serving as diagnostic markers or delivering therapeutic molecules to the exact spot in the body where the drug is intended to act. Before being applied to the medical field, however, nanoparticles must prove that they are safe for the human body and are capable of bypassing the immune system.
"Researchers can spend years developing a nanoparticle, without knowing what impact it will have on a living organism," says Carole Bourquin, professor in the medicine and science faculties at UNIGE and project leader. "So there was a real need to design an effective screening method that could be implemented at the beginning of the development process. Indeed, if the nanoparticles aren't compatible, several years of research were simply thrown away."
When any foreign element enters the body, including nanoparticles, the immune system is activated. Macrophages are always found on the front line; these are large cells that "ingest" invaders and trigger the immune response. The way macrophages react to the nanoparticle under investigation then determines the biocompatibility of the product.
"When you begin to develop a new particle, it's very difficult to ensure that the recipe is exactly the same every time," points out Inès Mottas, first author of the paper. "If we test different batches, the results may differ. Hence our idea of finding a way to test three parameters simultaneously – and on the same sample – to establish the product's biocompatibility: its toxicity, its ability to activate the immune system and the capacity of the macrophages to ingest them."
The ideal medical nanoparticle should therefore not be toxic (it should not kill the cells); should not be completely ingested by the macrophages (so that it retains its ability to act); and should limit the activation of the immune system (to avoid adverse side-effects).
Until now, evaluating the biocompatibility of nanomaterials was a laborious task that took several months and posed reproducibility problems, since not all the tests were performed on the same batch of particles. Bourquin and her team have now used flow cytometry with macrophages to determine the three essential elements in a safe and standardized manner, and in record time.
"The macrophages are brought into contact with the nanoparticles for 24 hours, and are then passed in front of the laser beams. The fluorescence emitted by the macrophages makes it possible to count them and characterize their activation levels," explains Mottas. "Since the particles themselves are fluorescent, we can also measure the amount ingested by the macrophages. Our process means we can test the three elements simultaneously, and we only need a very small amount of particles. We can obtain a comprehensive diagnosis of the nanoparticle submitted to us in two or three days."
This method is now part of the work carried out within the National Centres of Competence in Research (NCCR) ‘Bio-Inspired Materials’, and is already a great success with scientists striving to develop new particles, allowing them to select the most promising particles quickly. As well as having a financial impact on the cost of research, this new approach also limits the use of animal testing. Furthermore, it is opening the door to the increasingly personalized treatment of certain pathologies. For example, by testing the nanoparticles on tumor cells isolated from a particular patient, it should theoretically be possible to identify the most effective treatment for that patient.
This story is adapted from material from the University of Geneva, with editorial changes made by Materials Today. The views expressed in this article do not necessarily represent those of Elsevier. Link to original source.