The research team led by Prof. Jin Yong Lee of the Department of Chemistry (co-first author Ph. D. Jong Hyeon Lim) has developed a new lutetium texaphyrin photosensitizer (PS) system, LuCXB for Immuno-photodynamic therapy (IPDT) through collaborative research with research teams led by Prof. Dixian Luo (Huazhong University of Science and Technology Union Shenzhen Hospital), Prof. Quan Liu (Huazhong University of Science and Technology Union Shenzhen Hospital), Jonathan L. Sessler (University of Texas), and Prof. Jong Seung Kim (Korea University). The research was published in Journal of the American Chemical Society (IF: 14.4) in July 2024 under the title "Lutetium Texaphyrin-Celecoxib Conjugate as a Potential Immuno-Photodynamic Therapy Agent."

Conventional photodynamic therapy (PDT) is a promising non-invasive treatment for cancer; however, it has shown limitations such as reduced therapeutic efficiency due to hypoxia around cancer cells, inhibition of reactive oxygen species (ROS) generation, and failure to completely remove tumors or prevent recurrence and metastasis. This study addresses these limitations by exploring methods to enhance PDT efficacy through the conversion of ROS generation mechanisms and integrating immunotherapy to prevent cancer recurrence.

The LuCXB system developed in this study utilizes the Lutetium texaphyrin structure, which selectively accumulates in tumor tissues, allowing it to effectively target the cancer cells. By interacting with the Celecoxib structure in an aqueous environment, the system shifts ROS generation from the type II mechanism to the type I mechanism, thereby enhancing ROS generation efficiency even in hypoxic conditions. Professor Lee's team used non-adiabatic molecular dynamics (NAMD) simulations and density functional theory (DFT) calculations to elucidate the folding structure and corresponding energy state changes in an aqueous environment, providing theoretical insights into the ROS generation mechanism shift. They also confirmed differences in ROS generation efficiency from a kinetic perspective when compared to reference systems. The newly developed photosensitizer in this study is expected to contribute to the advancement of photodynamic therapy for cancer treatment.

*Title:Lutetium Texaphyrin-Celecoxib Conjugate as a Potential Immuno-Photodynamic Therapy Agent.