Ferrocene-Conjugated Paclitaxel Prodrug for Combined Chemo-Ferroptosis Therapy of Cancer.
Shaojin LuDengyuan HaoQian MengBiyou ZhangXiujuan XiangQing PeiZhigang XiePublished in: ACS applied materials & interfaces (2024)
Herein, we developed a paclitaxel prodrug (PSFc) through the conjugation of paclitaxel (PTX) and ferrocene via a redox-responsive disulfide bond. PSFc displays acid-enhanced catalytic activity of Fenton reaction and is capable of forming stable nanoparticles (PSFc NPs) through the assembly with distearoyl phosphoethanolamine-PEG 2000 . After being endocytosed, PSFc NPs could release PTX to promote cell apoptosis in response to overexpressed redox-active species of tumor cells. Meanwhile, the ferrocene-mediated Fenton reaction promotes intracellular accumulation of hydroxyl radicals and depletion of glutathione, thus leading to ferroptosis. Compared with the clinically used Taxol, PSFc NPs exhibited more potent in vivo antitumor outcomes through the combined effect of chemotherapy and ferroptosis. This study may offer insight into a facile design of a prodrug integrating different tumor treatment methods for combating malignant tumors.
Keyphrases
- cancer therapy
- cell death
- drug delivery
- electron transfer
- drug release
- chemotherapy induced
- hydrogen peroxide
- wastewater treatment
- photodynamic therapy
- oxide nanoparticles
- papillary thyroid
- locally advanced
- combination therapy
- cell proliferation
- type diabetes
- squamous cell
- adipose tissue
- metabolic syndrome
- rectal cancer
- mesenchymal stem cells