Scientists at the University of Eastern Finland have developed a technique that lets them improve the coating of nanoparticles when using cell membranes. Cell membranes offer a lot of benefits as a coating for synthetic nanoparticles, including shielding from the immune system, prolonged circulation times and improved tumor accumulation. However, current approaches to coating nanoparticles with cell membranes often result in an incomplete covering.
These researchers realized that a simple technique involving adding some additional phospholipids during production was enough to increase the membrane fluidity of the coating, allowing it to fuse and spread over the nanoparticle more easily. This translated to increased tumor accumulation in an animal model.
Nanoparticles are at the forefront of advanced drug delivery techniques. These tiny objects can zip through our vasculature to reach a target site, and for many researchers, tumors are a particularly exciting target for nanoparticle therapeutics. However, to reach their target safely and produce a therapeutic effect, the nanoparticles need to sneak past the immune system. This is no easy feat, as our immune system is highly attuned to recognize and destroy foreign objects in our body, and so researchers are constantly trying to improve on techniques that can shield such particles.
One approach involves taking a sample of cells, lysing them, and using their membranes to coat the nanoparticles. On the face of it, this makes a lot of sense, as the immune system may be tricked into thinking that the coated particles are merely small cells. However, in reality, this coating process is hit or miss, with the researchers calculating that only 6% of the particles receive a full coating and the others obtain only a patchy coating, limiting the protection the membrane provides.
These researchers hit on the simple idea of incorporating additional phospholipids, the basic building blocks of the cell membrane, during the nanoparticle coating procedure, with the aim of improving the patchy coating by increasing membrane fluidity. The team found that this allowed various patches of the membrane on the particle surface to fuse together more effectively, dramatically improving the particle coverage.
So, how did this translate to targeting efficacy? In a mouse tumor model, the researchers found that more of the nanoparticles ended up at the tumor site when they had been coated using the new technique, compared with traditionally coated particles. The researchers hope that the approach will prove useful for a variety of nanoparticle types.
“We have confirmed the universality of this hybrid coating method using various core nanoparticles, such as mesoporous silica, gold, and poly(lactic-co-glycolic acid) (PLGA),” said Vesa-Pekka Lehto, a researcher involved in the study. “With deep understanding of the coating mechanism, our finding introduces a new era of better biomimetic nanovector design for advanced tumor targeting.”
Study in Nature Communications: Systematic design of cell membrane coating to improve tumor targeting of nanoparticles