functionalization
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KAIST research team develops clathrin assembly for targeted protein delivery to cancer cells
In order to effectively treat cancer without additional side effects, we need a way to deliver drugs specifically to tumor cells. Protein assemblies have been widely used for drug delivery in the field of cancer treatment, but to use them for drug delivery they must first be functionalized, meaning they must be bound to the protein that recognizes the target tumor cell and deliver a drug that kills it. However, the functionalization process of protein assemblies is very complex, inefficient, and limited to small-sized chemical drugs, which limits their real-life applicability.
On March 14, a KAIST research team led by Professor Hak-Sung Kim from the KAIST Department of Biological Sciences reported the development of a clathrin assembly that can specifically deliver drugs to cancer cells.
Clathrin assemblies transport materials efficiently through endocytosis in living organisms. They are formed by the self-assembly of triskelion units, which are composed of three heavy chains bonded with three light chains. Inspired by this mechanism, the research team designed a clathrin chain to facilitate the functionalization of tumor cell recognition proteins and toxin proteins in order to deliver drugs specifically to tumor cells. From this, the team created a new type of clathrin assembly.
Figure 1. (Upper) Schematic diagram of the development of a new clathrin assembly that simultaneously functionalizes two types of proteins (cancer cell recognition protein and toxin protein) on heavy and light chains of clathrin in a one-pot reaction (bottom, left) Electron microscopy image of clathrin assembly: formation of an assembly with a diameter of about 28 nanometers (bottom, right) Cancer cell killing effect of CLA: CLA functionalized with epidermal growth factor receptor (EGFR) recognition protein and toxin protein kills only the cancer cells that overexpress EGFR.
The newly developed clathrin assembly requires a one-pot reaction, meaning both the toxin and tumor-recognition proteins can be functionalized simultaneously and show high efficiency. As a result, this technique is expected to be used in a wide variety of applications in the fields of biology and medicine including drug delivery, vaccine development, and diagnosing illnesses.
In this research, an epidermal growth factor receptor (EGFR), a common tumor marker, was used as the recognition protein, allowing drug delivery only to tumor cells. The clathrin assemblies that were functionalized to recognize EGFR showed a bonding strength 900-times stronger than it normally would due to the avidity effect. Based on this finding, the research team confirmed that treatment with toxin-functionalized clathrin assembly led to effective cell death for tumor cells, while it showed no such effect on healthy cells.
This research by Dr. Hong-Sik Kim and his colleagues was published in Small volume 19, issue 8 on February 22 under the title, "Construction and Functionalization of a Clathrin Assembly for a Targeted Protein Delivery", and it was selected as the cover paper.
Figure 2. Cover Paper: This study was published in the international journal 'Small' on February 22nd, Volume 19, No. 8, and was selected as the cover paper.
First author Dr. Hong-Sik Kim said, “Clathrin is difficult to functionalize, and since it is extracted from mammals, realistic applications have been limited.” He added, “But the new clathrin assembly we designed for this research can be functionalized with two different types of proteins through a single-step reaction, and can be produced from E. coli, meaning it can become an applicable protein assembly technology for a wide range of biomedical fields.”
This research was funded by the Global Ph.D. Fellowship and the Mid-career Researcher Grant of the National Research Foundation.
2023.03.22 View 4026 -
2016 KAIST EEWS Workshop
The Energy, Environment, Water and Sustainability (EEWS) Graduate School of KAIST hosted a workshop entitled “Progress and Perspectives of Energy Science and Technology” on October 20, 2016. The workshop took place at the Fusion Hall of the KAIST Institute on campus.
About 400 experts in energy science and engineering participated in the event. Eight globally recognized scientists introduced the latest research trends in nanomaterials, energy theory, catalysts, and photocatalysts and led discussions on the current status and prospects of EEWS.
Professors Yi Cui of Stanford University, an expert in nanomaterials, and William A. Goddard of California Institute of Technology presented their research experiments on materials design and recent results on the direction of theory under the topics of energy and environment.
Dr. Miquel Salmeron, a former head of the Material Science Division of Lawrence Berkeley National Laboratory, and Professor Yuichi Ikuhara of Tokyo University introduced their analysis of catalysts and energy matters at an atomic scale.
Professor Sukbok Chang of the Chemistry Department at KAIST, a deputy editor of ACS Catalysis and the head of the Center for Catalytic Hydrocarbon Functionalizations at the Institute of Basic Science, and Professor Yang-Kook Sun of Energy Engineering at Hanyang University, who is also a deputy editor of ACS Energy Letters, presented their latest research results on new catalytic reaction development and energy storage.
The workshop consisted of three sections which addressed the design of energy and environment materials; analysis of energy and catalytic materials; and energy conversion and catalysts.
The EEWS Graduate School was established in 2008 with the sponsorship of the Korean government’s World Class University (WCU) project to support science education in Korea. Professor J. Fraser Stoddart, the winner of the 2016 Nobel Prize in Chemistry, was previously worked at the KAIST EEWS Graduate School as a WCU visiting professor for two years, from 2011 to 2013. Professor Ali Coskun, who was a postdoctoral researcher in the laboratory of Professor Stoddart, now teaches and conducts research as a full-time professor at the graduate school.
Dean Yousung Jung of the EEWS Graduate School said:
“This workshop has provided us with a meaningful opportunity to engage in discussions on energy science and technology with world-class scholars from all around the world. It is also a good venue for our graduate school to share with them what we have been doing in research and education.”
2016.10.20 View 10808 -
Professors Sukbok Chang and Jang-Wook Choi Receive the 2015 Knowledge Award from the Korean Government
The Ministry of Science, ICT and Future Planning (MISP) of the Republic of Korea announced the 2015 Knowledge Awards on October 20, 2015. Two KAIST professors received the award.
Established in 2009, the awards are presented to Korean scientists whose publications have contributed to the international science community. Specifically, the MISP used the two biggest science databases, Science Citation Index Expanded (SCIE) and Scopus, to identify ten highly cited papers ranked in the top 1% by total citations in the past ten years.
Professor Sukbok Chang of Chemistry (left in the picture below) is a global authority in the field of catalytic hydrocarbon functionalization. His paper entitled “Palladium-catalyzed C-H Functionalization of Pyridine N-Oxides: Highly Selective Alkenylation and Direct Arylation with Unactivated Arenes,” which was published in the Journal of the American Chemical Society in 2008, was once selected by Thomson Reuters as one of the “Most Influential Research Papers of the Month.” In 2011, the American Chemical Society included his paper in the list of the top 20 research papers that were most frequently cited in the last three years.
Professor Jang-Wook Choi of the Graduate School of EEWS (Energy, Environment, Water, and Sustainability) has been known for his leading research in rechargeable battery, supercapacitor, and materials chemistry. In particular, his work on secondary fuel cells attracted significant attention from academia and industry in Korea. Professor Choi developed a super-thin flexible lithium-ion battery this year, thinner than a credit card, which lasts longer than the existing batteries and with greater performance. He also developed new electrode materials for next-generation sodium-ion and magnesium secondary fuel cells.
Professor Sukbok Chang (left) and Professor Jang-Wook Choi (right)
2015.10.23 View 9882