A team of researchers from the University of Melbourne’s Caruso Nanoengineering Group has developed an innovative drug delivery system with significant potential to revolutionize drug development. The new system, known as a metal–biomolecule network (MBN), consists of a coordination network made up entirely of metal ions and biomolecules, eliminating the need for complex drug “carriers.” This breakthrough could offer a simpler, more efficient, and safer alternative for a wide range of biomedical applications.
Published in Science Advances, the research was led by Melbourne Laureate Professor and NHMRC Leadership Fellow Frank Caruso, from the Department of Chemical Engineering, along with Research Fellows Dr. Wanjun Xu and Dr. Zhixing Lin, who share first authorship. The MBN nanoparticles are created by combining non-toxic metal ions (such as calcium and iron, which are naturally absorbed through the diet) with phosphonate biomolecules like DNA. These nanoparticles are chemically and metabolically stable, and have demonstrated antiviral, antibacterial, antifungal, anti-inflammatory, and anti-cancer properties.
Dr. Zhixing Lin explained that one of the most promising aspects of the MBN system is its potential to improve the success rate of drug development. Unlike traditional drug carriers, which can be toxic and provoke immune responses, the MBN system uses materials that are highly compatible with the human body. This could reduce the risks associated with drug delivery and increase the likelihood of success in clinical applications, especially for treatments like cancer therapies or gene delivery.
“We’ve developed functional metal-organic networks that can efficiently deliver biomolecule-based drugs for a range of biomedical applications, including anti-cancer, anti-viral therapies, immunotherapy, biosensing, bioimaging, and drug delivery,” Dr. Lin noted.
The challenge with traditional drug carriers is that many are made from materials that can be toxic or provoke an immune response, reducing their effectiveness. Dr. Wanjun Xu pointed out that, in drug development, only about one in 10,000 drug compounds reaches market approval. This high failure rate is often due to safety concerns, with extra non-functional components in drug carriers potentially increasing toxicity.
A key hurdle that the researchers overcame was ensuring that “free” biomolecular cargoes can effectively reach their target cells to achieve the desired biological effect. Over the course of a two-year project, the team minimized the need for extra components and created a simpler material system with greater potential for success, all while maintaining the necessary therapeutic performance.
The MBN nanoparticles can be engineered to activate at specific locations in the body, enhancing their effectiveness. For example, in the acidic microenvironment of tumors, such as those associated with breast cancer, the engineered nanoparticles could disassemble upon exposure to the low pH, targeting the tumor site precisely.
Professor Caruso emphasized that the MBN system is “tuneable,” meaning it can be customized for various biomedical applications. By selecting different biomolecules, metal ions, and assembly conditions, researchers can adjust the size, cargo, and targeting potential of the nanoparticles, allowing for a modular approach to creating multifunctional nanoparticles with diverse compositions. This flexibility opens up possibilities for developing a wide range of treatments, as well as applications in environmental science, where biological barriers to delivery also present challenges.
“Our system provides valuable insights into fundamental assembly mechanisms and will enable the creation of a library of bioactive nanoparticles that can be used in biomedicine and beyond,” Professor Caruso said.
The next phase of the team’s research will focus on further understanding the MBN system and testing it for advanced material formulations aimed at treating diseases. With its potential to improve drug development, enhance therapeutic efficacy, and minimize safety concerns, this new drug delivery system promises to be a game-changer in the field of biomedicine.
By Impact Lab
