Implementation of a Smart System for Targeted Therapy
A research team at Ajou University has developed a technology that can precisely control the timing and location of drug release in a biological environment. This technology is expected to be utilized in precision drug delivery and bioimaging applications.
Ajou University research team has developed a technology that can precisely control the release time and location of drugs in a biological environment. On May 27, Ajou University announced that a joint research team led by Professors Kim Eunha, Kim Uk, and Yoo Taehyun from the College and Graduate School of Advanced Bio-Convergence and the Department of Molecular Science and Technology has developed a simple and efficient method for synthesizing a biocompatible linker compound called bis-hydroxy trans-cyclooctene (C2TCO).
This research, titled "Facile Synthesis and Application of the Bioorthogonal Click-to-Release Reagent C2TCO for Multiplexed Immunofluorescence Imaging," was selected as the cover article for the May online edition of the prestigious journal Bioconjugate Chemistry.
The study was co-first authored by Dr. V. Arun, a postdoctoral researcher at the Department of Molecular Science and Technology, as well as graduate students Lee Minju, Choi Hongseo, and Lee Sangwoo, who are enrolled in the integrated master's and doctoral program. Professors Kim Eunha, Kim Uk, and Yoo Taehyun served as corresponding authors, and Professor Choi Junwon from the College and Graduate School of Advanced Bio-Convergence and the Department of Molecular Science and Technology participated as a co-author.
This achievement represents a significant advancement in the "click-to-release" reaction technology, which has recently attracted global attention in the field of bioorthogonal click chemistry. Bioorthogonal click chemistry is a "smart chemical technology" that enables only the desired reactions to occur, independent of the complex chemical reactions taking place within the human body.
The Ajou University research team implemented a simpler and more efficient version of the conventional click-to-release system. They succeeded in synthesizing the biocompatible linker compound bis-hydroxy trans-cyclooctene (C2TCO), an improved version of trans-cyclooctene (TCO) that has been used in click-to-release reactions, in a straightforward and stable manner.
Through this, they demonstrated the feasibility of "multi-cycle immunofluorescence imaging," which involves repeatedly staining, signal removal, and restaining a single cell sample with various antibodies. This bioimaging technique allows for the sequential visualization of dozens of proteins in a single tissue, thereby enabling more precise disease analysis.
In addition, the team developed an antibody-drug conjugate (ADC) by linking a cytotoxic drug (MMAE) to a therapeutic antibody (Atezolizumab) that targets the PD-L1 protein on the surface of cancer cells. This conjugate allows for precise drug release only at the target site upon treatment with tetrazine, thereby reducing side effects and maximizing therapeutic efficacy.
Professor Kim Eunha, who led the research, stated, "This study marks the first step toward the practical application of precise activation control technology for antibody-payload conjugates in biological environments using the click-to-release system." She added, "Although this is currently at the basic research stage, we anticipate that further expansion of related studies will allow for applications in various fields, including cancer treatment and precision diagnostics." She also said, "We plan to develop a variety of biodegradable compounds using bis-hydroxy trans-cyclooctene (C2TCO) and conduct follow-up research to apply this technology to various delivery systems beyond antibodies."
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