A lipid droplet-specific near-infrared automatic oxygen-supplied AIEgen for photodynamic therapy and metastasis inhibition of hypoxic tumors
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 O 2 −• was also clarified according to in vivo experiments, which indicated it could initiate a series of O 2 −• -mediated bio-catalytic reactions to gain autonomously generated O 2 inside solid tumors. TTIMN NPs sensitized O 2 −• formation even under severe O 2 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 O 2 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.
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