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Mitochondrial targeted AIEgen phototheranostics for bypassing immune barrier via encumbering mitochondria functions

Pai Liu1, Fei Ren2, Subin Son3

  • 1Beijing Key Laboratory of Construction Tailorable Advanced Functional Materials and Green Applications, School of Materials Science and Engineering, Beijing Institute of Technology, Beijing, 100081, China; State Key Laboratory of Separation Membranes and Membrane Processes, School of Chemistry, Tiangong University, Tianjin 300387, China; Department of Chemistry, Korea University, Seoul, 02841, Republic of Korea.

Biomaterials
|February 26, 2022
PubMed

Insights

This study introduces novel photosensitizers that combine photodynamic therapy with immunogenic cell death. This dual approach targets mitochondria-related damage-associated molecular patterns (DAMPs), effectively eliminating tumors and offering a new avenue for cancer immunotherapy.

Area of Science:

  • Biochemistry
  • Immunology
  • Oncology

Background:

  • Photodynamic therapy (PDT) combined with immunogenic cell death (ICD) shows promise for overcoming tumor recurrence and treatment resistance.
  • Existing research primarily focuses on endoplasmic reticulum (ER)-stressed damage-associated molecular patterns (DAMPs), neglecting mitochondria-related DAMPs.

Purpose of the Study:

  • To develop novel photosensitizers for combined PDT and ICD.
  • To investigate the role of mitochondria-related DAMPs, specifically TFAM (mitochondrial transcription factor), in cancer treatment.

Main Methods:

  • Synthesis of two intersystem crossing photosensitizers utilizing multiarylpyrrole structures.
  • Application of the developed photosensitizers in a tumor model.
  • Evaluation of tumor response and immunogenic effects.

Main Results:

  • The novel photosensitizers effectively induced tumor regression when combined with ICD.
  • Mitochondria-related DAMP-TFAM was identified as a key factor under oxidative stress during treatment.
  • The combined therapy demonstrated significant advantages over single-agent treatments.

Conclusions:

  • The study highlights the significance of mitochondria-related DAMPs, particularly TFAM, in enhancing PDT and ICD efficacy.
  • This research offers a new therapeutic strategy by targeting mitochondria-related DAMPs, addressing limitations of ER-stressed DAMP-focused approaches.
  • The findings provide an innovative target for developing novel cancer immunotherapies.
Keywords:
Aggregation-induced emission photosensitizersImmune barrierImmunogenic cell deathMitochondria-related damage-associated molecular patterns

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