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Triphenylphosphonium-based mitochondrial targeting in cancer therapy: mechanisms, progress, and perspectives

Min Yang1, Jiaming Ou1, Haibo Yan1

  • 1Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Innovative Drug Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331, P. R. China. zhangsl@cqu.edu.cn.

Chemical Communications (Cambridge, England)
|November 14, 2025
PubMed

Insights

Triphenylphosphonium (TPP)-based anticancer agents target mitochondria, enhancing cancer therapy selectivity. Future research focuses on multifunctional TPP molecules and novel delivery systems for improved clinical translation in precision oncology.

Area of Science:

  • Mitochondrial biology
  • Cancer therapy
  • Drug delivery

Background:

  • Mitochondria play crucial roles in cancer metabolism, apoptosis, and drug resistance.
  • Targeting mitochondria is a promising strategy for developing novel anticancer therapies.
  • Triphenylphosphonium (TPP)-based compounds leverage mitochondrial membrane potential for selective cancer cell accumulation.

Purpose of the Study:

  • To review recent advancements in TPP-based anticancer agents.
  • To summarize their mechanisms of action and current challenges.
  • To highlight future research directions for TPP-mediated mitochondrial therapies.

Main Methods:

  • Review of recent scientific literature on TPP-based anticancer agents.
  • Analysis of TPP compound mechanisms, focusing on mitochondrial targeting.
  • Identification of challenges and future research opportunities in the field.

Main Results:

  • TPP-based strategies show potential for selective accumulation in cancer cells.
  • Various TPP-based agents are under development for cancer treatment.
  • Integration with other therapies and advanced delivery systems are key areas of progress.

Conclusions:

  • TPP-based mitochondrial targeting offers a versatile platform for precision cancer therapy.
  • Future directions include multifunctional TPP molecules, combination therapies (e.g., immunotherapy), and smart delivery systems.
  • These advancements are expected to accelerate the clinical translation of TPP-mediated mitochondrial therapies for improved oncology outcomes.

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