Researchers have created flower-shaped particles that efficiently deliver drugs to targeted areas in the body. These particles are trackable and controllable via medical imaging techniques, and show promise for treating cancer and cardiovascular diseases after successful initial tests on mice.
Scientists have been searching for ways to deliver medicines to specific targets in the body for many years. Consider, for example, delivering cancer drugs directly to a tumor, ensuring they only take effect at this specific location without causing side effects in the rest of the body. Research is underway to identify carrier particles to which active ingredients can be bound.
These particles must satisfy certain requirements, including the following three: firstly, they must be able to absorb as many molecules of the active substance as possible; secondly, it must be possible to guide them through the bloodstream using a simple technique such as ultrasound; and thirdly, it must be possible to track their journey through the body with a non-invasive imaging procedure. This final point is the only way to verify whether the medicines have been successfully delivered.
Advancements in Particle Design for Medicine
Finding a single solution meeting all these requirements has been challenging. However, a research team led by ETH Zurich has introduced a special class of particle meeting all these criteria. These particles are not only effective, but they also look visually striking under a microscope, resembling tiny paper flowers or desert roses. They are composed of extremely thin petals that arrange themselves into flowers. These flower particles are one to five micrometers in diameter, slightly smaller than a red blood cell.
Their shape has two main advantages. Firstly, the flower particles have an enormous surface area in relation to their size. The spaces between the many densely packed flower petals are only a few nanometres wide and act like pores. This means they can absorb very large amounts of therapeutically active substances. Secondly, the flower petals scatter sound waves, or they can be coated with molecules that absorb light and thus can easily be made visible using ultrasound or optoacoustic imaging.
These findings have been reported by the groups led by Daniel Razansky and Metin Sitti in a study published in Advanced Materials. Razansky is a Professor of Biomedical Imaging with a double appointment at ETH Zurich and the University of Zurich. Sitti is an expert in micro-robotics and, until recently, was a professor at ETH Zurich and the Max Planck Institute for Intelligent Systems in Stuttgart prior to moving to Koç University in Istanbul.
Potential Applications and Future Research
“Previously, researchers primarily investigated tiny gas bubbles as a method of transport through the bloodstream using ultrasound or other acoustic methods,” said Paul Wrede, co-author of the study and doctoral student in Razansky’s group. “We have now demonstrated that solid microparticles can also be acoustically guided.” The advantage of the flower particles over the bubbles is that they can be loaded with larger quantities of active ingredient molecules.
The researchers demonstrated that the flower particles could be loaded with a cancer drug in Petri dish experiments. They also injected the particles into the bloodstreams of mice. Using focused ultrasound, they were able to keep the particles in a pre-determined position within the circulatory system. This was successful despite the rapid blood circulation surrounding the particles. Focused ultrasound is a technique whereby sound waves are concentrated at a localized spot. “In other words, we don’t just inject the particles and hope for the best. We actually control them,” said Wrede. The researchers are hoping that this technology will one day be used to deliver medicines to tumors or clots that block blood vessels.
The particles may be made from a variety of materials and have different coatings depending on what they are being used for and the researchers’ preferred imaging procedure for controlling the position of the particles. “The underlying working principle is based on their shape, not the material they are made from,” said Wrede. In their study, the researchers investigated flower particles made of zinc oxide in detail. They also tested particles made of polyimide and a composite material consisting of nickel and organic compounds.
Now, the researchers would like to refine their concept. They plan to conduct more animal tests first, after which the technology may benefit patients with cardiovascular disease or cancer.
Reference: “Hierarchical Nanostructures as Acoustically Manipulatable Multifunctional Agents in Dynamic Fluid Flow” by Dong Wook Kim, Paul Wrede, Hector Estrada, Erdost Yildiz, Jelena Lazovic, Aarushi Bhargava, Daniel Razansky and Metin Sitti, 14 October 2024, Advanced Materials.
DOI: 10.1002/adma.202404514
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