Triphenylphosphonium Functionalization Enables Efficient Mitochondrial Targeting of HPMA Copolymers

This article presents a comprehensive study describing the use of triphenylphosphonium (TPP) groups as a strategic modification for water‐soluble polymer systems aimed at targeting mitochondria. By conjugating TPP to polymers based on N ‐(2‐hydroxypropyl)methacrylamide, we exploit the unique properties of TPP to promote selective accumulation within the mitochondrial matrix. We describe the synthesis, characterization, and optimization of TPP groups content per polymer chain, demonstrating its potential to improve polymer‐ drug delivery to mitochondria. The results of this work demonstrate the possibility of active targeting of polymer systems, which can be used as a valuable tool for targeted delivery of drugs whose effect is related to mitochondrial function.