A protein-conjugated photosensitizer with mitochondrial targeting for enhanced photodynamic therapy

Mingwan Shi1, Wei Pan1, Peng Gao1

  • 1College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative InnovationCenter of Functionalized Probes for Chemical Imaging in Universities of Shandong Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014, P. R. China. panwei@sdnu.edu.cn.

Chemical Communications (Cambridge, England)
|October 3, 2022
PubMed

Insights

This study developed a targeted photosensitizer to improve photodynamic therapy (PDT) efficacy. The new compound effectively induces cell death by disrupting mitochondrial function through reactive oxygen species generation.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Photodynamic Therapy

Background:

  • Photodynamic therapy (PDT) is a promising cancer treatment modality.
  • Enhancing the specificity and efficacy of PDT remains a critical challenge.
  • Mitochondria are key targets for inducing irreversible cancer cell death.

Purpose of the Study:

  • To synthesize a novel protein-conjugated photosensitizer.
  • To imbue the photosensitizer with mitochondrial targeting capabilities.
  • To evaluate its enhanced therapeutic potential in PDT.

Main Methods:

  • Synthesis of a protein-conjugated photosensitizer.
  • In vitro assessment of reactive oxygen species (ROS) generation under laser irradiation.
  • Analysis of intracellular protein damage and mitochondrial function.
  • Evaluation of cell viability and induction of apoptosis.

Main Results:

  • The synthesized photosensitizer demonstrated efficient ROS production upon laser activation.
  • Targeted delivery to mitochondria was confirmed.
  • Significant disruption of mitochondrial redox homeostasis and key protein function was observed.
  • Irreversible cell death was induced in cancer cells.

Conclusions:

  • Protein-conjugated, mitochondrially-targeted photosensitizers represent a potent strategy for enhancing PDT.
  • This approach effectively leverages ROS to induce targeted cell death via mitochondrial disruption.
  • Further investigation is warranted for clinical translation of this enhanced PDT approach.