A lipid droplet-specific near-infrared automatic oxygen-supplied AIEgen for photodynamic therapy and metastasis inhibition of hypoxic tumors

• Published in: Chemical engineering journal (Lausanne, Switzerland : 1996) Switzerland : 1996), 2023-02, Vol.453, p.139838, Article 139838
• Main Authors: Wang, Xing, Tang, Yuqi, Liang, Jiankang, Zhao, Yongfei, Yang, Li, Qi, Zhengjian
• Format: Article
• Language: English
• Subjects: AIEgens; Automatic oxygen-supplied; Hypoxia; Lipid droplet; Near-infrared
• ISSN: 1385-8947; 1873-3212
• DOI: 10.1016/j.cej.2022.139838

[Display omitted] •TTIMN NPs targeted lipid droplet to deplete GSH and inactivate GPX4.•TTIMN NPs induced cytochrome c release and activated the apoptosis pathway.•TTIMN NPs initiated O2−•-mediated bio-catalytic reactions to generate O2.•TTIMN NPs sensitized O2−• formation even under severe O2 shortage environment.•Self-generated O2 fluctuated HIF-related signaling and DNA methylation. TTIMN NPs prepared based on TTIMN has the function of targeting lipid droplet to induce tumor regression by depleting GSH and inactivating GPX4. Meanwhile, the mode of TTIMN NPs catalyzed the conversion of O2−• was also clarified according to in vivo experiments, which indicated it could initiate a series of O2−•-mediated bio-catalytic reactions to gain autonomously generated O2 inside solid tumors. TTIMN NPs sensitized O2−• formation even under severe O2 shortage environment, and a part of it would be converted into highly toxic OH•, subsequently triggering the release of cytochrome c and activating the cascade of the Caspase family that ultimately led to cell apoptosis. Self-generated O2 inhibited tumor proliferation and metastasis mainly by interfering with HIF-related signaling and downregulating DNA methylation. TTIMN NPs has less systemic toxicity in blood systems and no effect on major organs, and blocked tumor progression by maintaining self-metabolism and immune system stability.