“As Much As Desired at the Preferred Time!”
A system for modulating peptide accessibility was developed.
The system can contribute to patient-customized immunotherapy through the remote control of peptide accessibility.
The research results of Professor Kang Hee-min were published in the Journal of the American Chemical Society as a cover article.

▲ (Left) Kim Yu-ri (first author, a student in the Master’s and Doctoral Degree Combined Program) and (right) Professor Kang Hee-min (corresponding author).

Professor Kang Hee-min’s group in the Department of Materials Science and Engineering at Korea University (KU President, Chung Jin Taek) developed a system capable of controlling the immune responses in the body through the remote control of peptide accessibility.
* Title of article : Manipulating Nanoparticle Aggregates Regulates Receptor-Ligand Binding in Macrophages

The results obtained by Professor Kang Hee-min’s group (first author: Kim Yu-ri, a student in the Master’s and Doctoral Degree Combined Program) were published online in the Journal of the American Chemical Society (IF: 15.419) as a cover article on March 12.

* This study was supported by the Basic Research Program (New Researcher Program) funded by the Ministry of Science and ICT and the National Research Foundation of Korea.


▲A schematic representation of the peptide accessibility control system depending on the size of the inorganic nanoparticle aggregate materials and remote control of their height.

There are many stages from immune response to tissue healing; therefore, effective immunotherapy requires appropriate control of the immune responses at each stage.

Previous studies have attempted to control the immune response by using external stimuli, including pH change, ultrasound, and light, but it was difficult to control the cellular responses reversibly. In addition, the external stimuli or materials used in the previous studies were not biocompatible and thus may be harmful to the body. Other studies attempted to control the immune responses by using a biocompatible external magnetic field, but the dichotomous control of the peptide accessibility limited the overall control of diverse immune responses.

To control the body’s immune responses by means of a biocompatible system with various modes, Professor Kang’s group bound cell-adhesive peptides onto the surface of biomaterials and attached ‘external stimuli-sensitive inorganic nanoparticle aggregate materials’ that can be synthesized in various sizes. The research group found that attaching the inorganic nanoparticle aggregate materials onto the biomaterial surface of the same cell-adhesive peptide density allowed for the control of the peptide accessibility depending on the size of the inorganic nanoparticle aggregate materials.

In addition, they found that the peptide accessibility can be controlled by regulating the height of the inorganic nanoparticle aggregate materials on the biomaterial surface by using a permanent magnet to govern the macrophage behavior, which plays a critical role in early immune responses.

The research group overcame the limitations of the previous studies by applying various sizes of inorganic nanoparticle aggregate materials and reversibly controlling their motion with a permanent magnet. Furthermore, the group proposed accessible peptide density as a new parameter for the control of the bonding between the cellular receptors and peptides, presenting a new reference for future studies on the immune system.

※ Terms
* Peptide : A peptide is a polymer of amino acids. Depending on the amino acids, a peptide specifically binds to a cellular receptor in the body to activate or inhibit various functions.
* Bendy linker: A bendy linker refers to a poly(ethylene glycol) polymer that is used to couple inorganic nanoparticle aggregate materials with a biomaterial surface. The bendy linker is an apparatus for the reversible control of the position of the inorganic nanoparticle aggregate materials depending on the position or presence of a permanent magnet.
* External stimuli-sensitive inorganic nanoparticle aggregate materials: These materials are aggregates of superparamagnetic iron oxide (Fe3O4) nanoparticles, the size of which can be controlled according to the need. Superparamagnetism, a property of magnetic nanoparticles, refers to the material being magnetized by the application of a magnetic field, with the magnetism being undone by the removal of that magnetic field. This property is required to remotely control nanoparticles.
*Macrophage: Macrophages play an important role in early immune responses. A macrophage is polarized into an M1 or M2 macrophage by the external environment. The M1 macrophage, having proinflammatory characteristics, plays a critical role in defending our body from the bacteria that can invade it, while the M2 macrophage is involved in anti-inflammatory responses and tissue remodeling. The polarization of macrophages is actively studied, since it can control the phases of inflammatory diseases.