The Korea Advanced Institute of Science and Technology (KAIST) said on Tuesday that its researchers have developed a clathrin assembly that can specifically deliver drugs to cancer cells for a wide variety of biomedical applications.

Cancer is often difficult to treat because drug delivery systems that can effectively target cancer cells without side effects are difficult to achieve. Protein assemblies are widely used in drug delivery for cancer treatment whereby the protein should bind to cancer cells and release a drug that kills cancer cells.

However, this functionalization process of protein assemblies is very complicated, inefficient, and limited to the application of small-sized chemical drugs.

Naturally in the body, a protein assembly called clathrin is self-assembled in cells to efficiently transport substances. The clathrin assembly is formed by combining three heavy chains and three light chains to form a triskelion.

Using this principle, the research team led by Professor Kim Hang-suk of KAIST's Department of Biological Sciences designed a new clathrin chain to facilitate the functionalization of cancer cell recognition proteins and toxin proteins to deliver drugs specifically to cancer cells.

In this study, a protein that recognizes epithelial cell growth factor receptor (EGFR), a representative tumor marker, was used to deliver drugs specifically to cancer cells. Clathrin assemblies functionalized to recognize EGFR proteins showed a significant 900-fold improvement in binding force compared to existing assemblies.

Consequently, the research team confirmed that when the clathrin assembly linking the toxin protein was treated on the cells, it did not affect normal cells, but effectively killed only cancer cells.

The developed clathrin assembly is dual-functionalized with a protein cargo and a targeting moiety through a "one-pot reaction" to simultaneously recognize cancer cells and toxins which are expected to be widely useful for drug delivery, vaccine development, and disease diagnosis in the future.

"As clathrin is difficult to functionalize and is obtained from mammalian cells, its practical application has been limited," said Kim Hong-sik, the first author of the study. “The newly designed clathrin assembly in this study can be converted into two different types of proteins in a single reaction, and can be produced in E. coli, making it a protein assembly application technology that can be widely used in the biomedical field.”

The study was published on the cover of the international journal, Small, on Feb. 22.