Two-Photon Photodegradation of E3 Ubiquitin Ligase Cereblon by a Ru(II) Complex: Inducing Ferroptosis in Cisplatin-Resistant Tumor Cells.
Xinlin LinMengsi ZhengKai XiongFa WangYu ChenLiangnian JiHui ChaoPublished in: Journal of medicinal chemistry (2024)
Using photodynamic therapy (PDT) to trigger nonconventional cell death pathways has provided a new scheme for highly efficient and non-side effects to drug-resistant cancer therapies. Nonetheless, the unclear targets of available photosensitizers leave the manner of PDT-induced tumor cell death relatively unpredictable. Herein, we developed a novel Ru(II)-based photosensitizer, Ru-Poma . Possessing the E3 ubiquitin ligase CRBN-targeting moiety and high singlet oxygen yield of 0.96, Ru-Poma was demonstrated to specifically photodegrade endogenous CRBN, increase lipid peroxide, downregulate GPX4 and GAPDH expression, and consequently induce ferroptosis in cisplatin-resistant cancerous cells. Furthermore, with the deep penetration of two-photon excitation, Ru-Poma achieved drug-resistant circumvention in a 3D tumor cell model. Thus, we describe the first sample of the CRBN-targeting Ru(II) complex active in PDT.
Keyphrases
- photodynamic therapy
- drug resistant
- cell death
- energy transfer
- cell cycle arrest
- multidrug resistant
- acinetobacter baumannii
- highly efficient
- fluorescence imaging
- single cell
- quantum dots
- poor prognosis
- cancer therapy
- induced apoptosis
- high glucose
- living cells
- pseudomonas aeruginosa
- cystic fibrosis
- papillary thyroid
- cell therapy
- cell proliferation
- squamous cell carcinoma
- stem cells
- diabetic rats
- stress induced
- endothelial cells