Theralase Technologies Inc. V.TLT

Today's TLD1433 Shout Out

[Eoganacht]

Uridine-Modified Ruthenium(II) Complex as Lysosomal LIMP-2 Targeting Photodynamic Therapy Photosensitizer for the Treatment of Triple-Negative Breast Cancer

Qiong Wu, Chanling Yuan, Jiacheng Wang, Guohu Li, Chunguang Zhu, Li Li, Zongtao Wang, Qingshuang Lv, and Wenjie Mei*

Guangdong Pharmaceutical University, Guangzhou, China

Publication Date:February 16, 2024

 

"...Ru(II) polypyridyl complexes possess the advantages of significant Stoke’s shift, strong spin coupling, efficient electron transfer, and rapid energy transfer. (19) After light excitation, Ru(II) complexes boost the effectiveness of intersystem crossing (ISC), allowing molecules to reach the excited triplet state that favors ROS production through electron or energy transfer using oxygen or water molecules as grist for generating toxins that eventuate in the death of tumor cells under hypoxic conditions. (20,21) In 2017, the first Ru-based photosensitizer, TLD1433, entered phase I clinical trials with effective PDT for non-muscle-invasive bladder cancer. (22) Additional studies have shown that Ru(II) polypyridyl complexes are able to function as lysosome-enriched photodynamic photosensitizers that inhibit tumor cell growth. (23−26) Peng et al. reported the synthesis of a red light-stimulated lysosome-targeted Ru(II) complex (Ru–I, [Ru(terpy)(Cl-7-IVQ)I]+), which exhibited significant therapeutic efficacy on breast cancer cells using radiation at 660 nm, both in vitro and in vivo. (27) Chao et al. designed and synthesized a Ru(II) polypyridyl complex within cell targeting lysosomes that demonstrated good water solubility. (28,29) This Ru(II) polypyridyl complex has good photostability and significant two-photon excitation efficiency, with high tumor kill rates. In addition, Mao et al. achieved targeted recognition of lysosomes by introducing nanocarbon-loaded polypyridine Ru(II) complexes. These effectively promote tumor cell death under light excitation. (30) Collectively, these studies suggest that lysosome-targeting Ru(II) complexes will have promising applications as photosensitizers for clinical PDT treatments."