Liposome encapsulated polydopamine nanoparticles: Enhancing ferroptosis and activating hypoxia prodrug activity

• Published in: Materials today bio Vol. 25; p. 101009
• Main Authors: Guo, Yijun, Luo, Huiling, Jiang, Hairong, Liu, Xinxin, Long, Xinrui, Hou, Yinuo, Chen, Zhou, Sun, Yanan, Ge, Dongtao, Shi, Wei
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-04-2024; Elsevier
• Subjects: Combination therapy; Ferroptosis; Full Length; Hypoxic activation prodrug; Lipid peroxidation; Unsaturated liposome; Lipid peroxidation; Hypoxic activation prodrug; Ferroptosis; Unsaturated liposome; Combination therapy
• ISSN: 2590-0064; 2590-0064
• DOI: 10.1016/j.mtbio.2024.101009

The short lifespan of active oxygen species and depressed O2 level during ferroptosis treatment in tumor cells weaken ferroptosis therapy. How to improve the utilization efficiency of active oxygen species generated in real time is pivotal for anticancer treatment. Herein, the tirapazamine (TPZ) loaded polydopamine-Fe nanoparticles (PDA-Fe-TPZ) was modified with unsaturated liposome (Lip), which was constructed to overcome the drawbacks of traditional ferroptosis therapy. The Lip@PDA-Fe-TPZ nanoliposomes can react with H2O2 to produce •OH by Fenton reaction, which then attacks Lip and transforms into radical intermediate (L•) and phospholipid peroxide radical (LOO•) to avoid the annihilation of •OH. The introduced Lip enhances lipid peroxidation and promotes oxygen consumption, resulting in increased hypoxia at tumor site. The introduced TPZ can be triggered by reductase in tumor cells under hypoxia, which can reduce to transient oxidative free radicals by reductase enzymes and destroy the structure of the surrounding biomacromolecules, thus achieving the synergistic treatment of ferroptosis and chemotherapy. In this work, we organically combined enhanced ferrroptosis with hypoxic activated chemotherapy to achieve efficient and specific tumor killing effect, which can sever as a promising treatment of cancer in the future.
The short lifespan of •OH and low •OH utilization efficiency of ferroptosis has become the main bottleneck restricting the therapeutic efficacy. This work developed a nanolipsome, which combined with hypoxia prodrug TPZ and a series of lipid peroxidation chain reactions, can promote the ferroptosis and chemotherapy treatment efficiency together. [Display omitted]
••OH attacks unsaturated liposomes (Lip) in situ and induces lipid peroxidation chain reactions to avoid the annihilation of •OH.•Through the transformation of free radicals, the expansion of ROS and the accumulation of lipid peroxides, the ferroptosis effect significantly enhanced.•Nanolipsomes coated with TPZ can transform hypoxia into a favorable condition, realizing organical combination of ferroptosis and chemotherapy.