Application Prospects of Triphenylphosphine-Based Mitochondria-Targeted Cancer Therapy

SIMPLE SUMMARY: Although there are various treatments for tumors, chemotherapy is still one of the most dominant and irreplaceable treatment modalities nowadays. Unfortunately, chemotherapy is often accompanied by serious toxic side effects. Therefore, the search for new targets for antitumor drug action and the synthesis of new antitumor drugs has been a major topic of research in cancer therapy. With the development of medical science, excellent anti-tumor drugs need not only good therapeutic effects and less toxic side effects, but also preferably lower doses that can achieve therapeutic effects. Organelle-targeted antitumor agents can meet these requirements and have become one of the hot spots for antitumor drug research nowadays, such as mitochondria-targeted antitumor drugs. This review focuses on the application of triphenylphosphine (TPP) in mitochondria-targeted drugs and summarizes the common mitochondria-targeted carriers currently available, in the hope of providing a reference for the development of better mitochondria-targeted agents for tumor therapy. ABSTRACT: Cancer is one of the leading causes of death and the most important impediments to the efforts to increase life expectancy worldwide. Currently, chemotherapy is the main treatment for cancer, but it is often accompanied by side effects that affect normal tissues and organs. The search for new alternatives to chemotherapy has been a hot research topic in the field of antineoplastic medicine. Drugs targeting diseased tissues or cells can significantly improve the efficacy of drugs. Therefore, organelle-targeted antitumor drugs are being explored, such as mitochondria-targeted antitumor drugs. Mitochondria is the central site of cellular energy production and plays an important role in cell survival and death. Moreover, a large number of studies have shown a close association between mitochondrial metabolism and tumorigenesis and progression, making mitochondria a promising new target for cancer therapy. Combining mitochondrial targeting agents with drug molecules is an effective way of mitochondrial targeting. In addition, hyperpolarized tumor cell membranes and mitochondrial membrane potentially allow selective accumulation of mitochondria-targeted drugs. This enhances the direct killing of tumor cells by drug molecules while minimizing the potential toxicity to normal cells. In this review, we discuss the common pro-mitochondrial agents, the advantages of triphenylphosphine (TPP) in mitochondrial-targeted cancer therapy and systematically summarize various TPP-based mitochondria-targeting anticancer drugs.