Final Report Summary - INTERACT-MEMNP (Interaction and actuation of lipid membranes with magnetic nanoparticles) The project InterAct-MemNP had as its goal to develop a better understanding of the interaction of nanoparticles designed for biomedical applications such as biomedical imaging and drug delivery with cells and cell membranes. Advances in this area will lead to technologies that improve our ability to e.g. detect cancer in the living body, direct imaging that improves surgical procedures and the possibility to localize drug delivery and avoid adverse side effects of medication. The latter would greatly reduce suffering patients, while also improving the efficacy of drugs. We approached this topic using nano-sized magnetic particles that are biocompatible materials with unique properties in their nanoscale form that allows us to image, steer transport of the particles and locally induce heat using magnetic fields to which the body is transparent. The first step was to understand how to design a shell around these nanoscale magnets such that they are invisible to cells in the body and thereby do not get detected by the many systems that serve to remove foreign materials from the blood stream. Generating the knowledge to solve this problem will simultaneously enable other applications such as separation and purification of proteins in biotechnology, detection and destruction of biofilms or even how to make new smart materials based on nanoparticle composites that are not biological, but where the challenge physically is the same. Our hypothesis was that by tuning the size and making a dense brush of polymers around the nanomagnets that mimic the properties of water, we can suppress binding to proteins and lipids, which in turn makes the particles impossible for cells to recognize. Indeed, it was possible for us to demonstrate that for several different polymers the structure of the polymer by which we coat the nanoparticles with decides whether a cell will recognize nanoparticles; this directly correlated with whether nanoparticles bound to lipid membranes and proteins. It was shown that the same properties that made the particles “stealth” led to much more efficient contrast agents for magnetic resonance imaging as well as provide a platform for functionalizing nanoparticles for targeting specific molecules and tissues. The fundamental work on nanoparticle synthesis that made these results possible, also led to several innovations in nanoparticle synthesis that are required for applications, such as synthesis of large amounts of particles that have identical properties and can be stored for long times. The research on understanding nanoparticle insertion into lipid (cell) membranes also made it possible for us to develop a type of drug delivery vehicle with nanomagnets incorporated in a cell-like membrane that acts like a shell to store drug molecules inside. By finding ways to precisely control the insertion of these nanomagnets we could show that the rate and amount of drug released can be controlled through magnetic fields that do not interact with the body. We continued by showing that this principle could be translated to nanoscale drug delivery vesicles that combine the robustness of synthetic polymer capsules with the versatility of biological (lipid) membranes, which could be used for novel, highly efficient localized drug delivery.The fundamental nature of our research on the influence of polymer structure on the interactions of nanoparticles with their environment also led to unexpected new insights and technologies. We applied ideas originally developed to improve synthesis and performance of nanoparticles for medical imaging to synthesize nanoparticles that can be used to reinforce composite (plastic) materials and give them new properties that these materials do not have today. This could greatly improve on materials currently used in, e.g. packaging, display and lighting technologies and demonstrates how fundamental research in one area can lead to potential breakthroughs in seemingly unrelated areas.
