Drug Delivery with Magnetically Guidable Mussel Proteins
– Professor Hyung Joon Cha’s research team at POSTECH develops magnetically guidable adhesive microbots using the mussel adhesive protein (MAP).
– The new device stays put for more than a week in environments like esophagus where fluids flow rapidly.
The esophagus is a highly dynamic conduit organ that passes water and food toward the gastrointestinal tract via coordinated muscle actions. Because of this, it is difficult to apply therapeutic drugs to a specific lesion site when esophageal disorders occur. The drugs fail to remain in the target site for a long period of time due to hydrodynamic shear force1 and drag force2.
To this, a POSTECH research team led by Professor Hyung Joon Cha (Ph.D. candidate Hyun Sun Choi) in the Department of Chemical Engineering in collaboration with Professor Yun Kee Jo of the Department of Biomedical Convergence Science and Technology at Kyungpook National University have together developed magnetically guidable mussel protein-based adhesive microbots. Magnetic guidance refers to the property of moving in the direction of a magnetic field in response to an external magnetic field.
The microparticles developed by Professor Cha’s team can control their movement in the direction in which a magnetic field is applied, and can provide locoregional delivery of therapeutic drugs to the targeted lesion site in dynamic fluid-associated conduit organs for a prolonged period.
Conventional magnetically guided drug delivery systems have a limitation in that drugs easily disappear in highly dynamic fluids environment of the body when the magnetic field is removed after the drugs are delivered to the target sites.
To this, the research team loaded iron oxide nanoparticles in the microparticles. They are then delivered locally to the lesion site primarily by the magnetic field in the passageway through which fast fluid flows. Thanks to the superior underwater adhesive properties of the mussel adhesive proteins, the microparticles remain at the site for a prolonged period even after the magnetic field is removed.
From experiments, the researchers confirmed that the delivery efficiency was 5.17 times higher in the presence of a magnetic field than the magnetic field-free conditions. In addition to the excellent biocompatibility of the microparticles, Professor Cha’s team experimentally verified their high anticancer effects by loading doxorubicin – a chemotherapy drug widely used for cancer treatment – in the microparticles to increase the cytotoxicity of cancer cells to about 84%. The therapeutic effects were maintained at the delivery site for long periods of time even after the magnetic field was removed. This is significant in that it demonstrates excellent therapeutic effects for patients with esophageal disorders even with a small dose of drugs and low frequency of administration. Due to the nature of these microparticles, their location can even be tracked in real time via magnetic resonance imaging3.
“The microbot therapeutics delivery system developed in this study is widely applicable in treating disorders that occur in organs that involve rapid fluid flow, such as the esophagus as well as the intestine,” explained Professor Cha on the significance of the research.
The findings from this study were published as the front cover paper of Advanced Functional Materials, a world-renowned academic journal in the field of materials science. The study was conducted with the support from the Mid-Career Researcher Program and the Young Researcher Program funded by Korea’s Ministry of Science and ICT, and the Korea Health Technology R&D Project funded by the Ministry of Health and Welfare of Korea.
1. Shear force
A force acting in parallel along a plane within an object when equal magnitude and opposite forces act simultaneously on an object. In particular, in fluid mechanics, it is also referred to as a deflection or shear stress.
2. Drag force
The resistant force exerted by a fluid when an object is moving or at rest in a flowing fluid, also called fluid resistance.
3. Magnetic resonance imaging (MRI)
A technique in which a device composed of magnets emits high-frequency waves to the human body to resonate hydrogen nuclei in body parts, and the difference in signals from each tissue is converted into digital information then visualized.