Tumor Selective Metabolic Reprogramming as a Prospective PD-L1 Depression Strategy to Reactivate Immunotherapy

Yu Liu, Zaigang Zhou, Jiting Hou, Wei Xiong, Heejeong Kim, Jiashe Chen, Chunjuan Zheng, Xin Jiang, Juyoung Yoon, Jianliang Shen

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Currently, the role of the lysosome, endoplasmic reticulum, or dictyosome in the transcription and translation of programmed cell death ligand 1 (PD-L1) is well revealed, but the role and function of mitochondria in the PD-L1 expression in tumors is still not fully researched, making it hard to offer a novel PD-L1 regulation strategy. In this research, it is newly revealed that mitochondria oxidative phosphorylation (OXPHOS) depression can be used as an effective PD-L1 down-regulation method. To offer an ideal and high-effective tumor mitochondria-targeted OXPHOS depression nanosystem, IR-LND is prepared by conjugating mitochondria-targeted heptamethine cyanine dye IR-68 with mitochondrial complexes I and II depression agent lonidamine (LND), which then further self-assembled with albumin (Alb) to form IR-LND@Alb nanoparticles. By doing this, PD-L1 expression in tumors is selectively and effectively depressed by IR-LND@Alb nanoparticles. As expected, the anti-tumor efficacy of such a PD-L1 depression strategy is superior to conventional anti-PD-L1 monoclonal antibodies. Interestingly, IR-LND can also be served as a novel ideal promising photodynamic therapy (PDT) drug with self-oxygen and self-PD-L1 regulation capacity. All in all, this tumor-selective metabolic reprogramming platform to reactivate immunotherapy and sensitize for PDT effect, would open a new window for mitochondrial immunotherapy for cancer patients.

Original languageEnglish
Article number2206121
JournalAdvanced Materials
Issue number41
StatePublished - 13 Oct 2022


  • immunotherapy
  • mitochondria
  • photodynamic therapy
  • programmed death ligand-1
  • tumor targeting


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