Mitochondria-targeted cancer therapy based on functional peptides

Mitochondria are critical for tumor growth and metastasis. A number of traditional antitumor drugs have poor water solubility and must penetrate multiple cellular barriers to reach the mitochondria. Because mitochondria have a unique transmembrane potential and an inner membrane with a low permeability, it is difficult for most drugs to enter mitochondria. In recent years, mitochondria-targeted delivery systems that use functional peptides to modify drugs have received increasing attention. Introducing functional peptides can change the original physicochemical properties of drugs and actively target mitochondria. Functional peptide-drug conjugates (PDCs, peptide-drug conjugates) can decompose and release drugs over time or due to certain stimuli in tumors. This preserves the biological activity of the drug while increasing intratumor uptake through the enhanced permeability and retention effect (EPR, the enhanced permeability and retention effect). In this review, we focus on the direction of cancer therapy and review the application of different functional peptides in the mitochondria-targeted tumor treatments reported in recent years.(c) 2023 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.