Research Projects

The proposed research aims to develop novel gold(III) [Au(III)] complexes as a new class of non-macrocyclic photosensitizers for cancer photodynamic therapy (PDT), addressing key limitations of clinically used agents such as Photofrin [1]. PDT employs a photosensitizer (PS), light, and tissue oxygen to generate reactive oxygen species (ROS) that selectively destroy cancer cells [2,3] (Figure 1(a), 1(b)). Despite its clinical promise, existing PDT agents suffer from poor photophysical properties, limited tumor selectivity, off-target toxicity, and high treatment cost [1–3]. Metal complexes have emerged as attractive alternatives [4,5], and the clinical evaluation of the Ru-based PDT agent TLD1433 has renewed interest in non-macrocyclic systems [6]. Au complexes have gained attention as anticancer agents due to their unique mechanisms of action and favorable redox properties [7,8]. Au(III), due to the heavy atom effect, can promote efficient intersystem crossing (ISC) and singlet oxygen generation (Figure 1(b)), which is central to type-II PDT [9]. Despite these advantages, Au(III) complexes remain virtually unexplored in PDT applications [9,10]. This work proposes to synthesize and evaluate a series of structurally diverse, non-macrocyclic Au(III) complexes bearing photoactive and bioresponsive ligands such as dppz and dppn, and BODIPY, glucose, and ferrocenyl-functionalized phenanthroline ligands (Figure 2(a)). These ligands are chosen/designed to improve photophysical performance, aqueous solubility, and cancer cell uptake, enabling passive or receptor-mediated accumulation. A mixed-ligand approach using N,N-donor bidentate, N,N,N-donor tridentate, S,S-donor bidentate, and O,O-donor bidentate ligands is proposed to stabilize the Au(III) center and fine-tune redox and photodynamic properties (Figure 2(b)). The central hypothesis is that rationally designed Au(III) complexes functionalized with photosensitizing and biologically responsive ligands can serve as efficient PDT agents under low-energy visible or red light. These complexes are expected to show enhanced singlet oxygen yield, improved photostability, and reduced systemic toxicity compared to existing agents. The work will involve synthesis, physicochemical characterization, and photophysical and redox profiling. Biological evaluation will include in vitro cytotoxicity assays in 2D cultures and 3D tumor spheroids. Mechanistic studies, such as ROS detection, apoptosis assays, and cellular imaging, will clarify the mode of cell death. Promising complexes will undergo ethically approved in vivo testing for safety and efficacy in tumor-bearing mice. The work is expected to advance the understanding of novel photoactive Au(III) complexes, contribute to the development of effective cancer PDT, and support national research priorities. It could also lead to IPR generation and provide a foundation for future research in this new area with clinical translation potential.