Conjugation of Triphenylphosphonium Cation to Hydrophobic Moieties to Prepare Mitochondria-Targeting Nanocarriers

The contribution of mitochondrial dysfunctions to diseases such as cancer, diabetes, cardiovascular, and neurodegenerative diseases has made mitochondria an attractive pharmacological target. To deliver biologically active molecules to mitochondria, however, cellular and mitochondrial barriers must be first overcome. The mitochondrial transmembrane electric potential (negative inside) is among the most commonly used strategies to deliver molecules to mitochondria as it allows the accumulation of positively charged molecules. Thus, therapeutic molecules are either covalently conjugated to lipophilic cations like triphenylphosphonium (TPP) or loaded into nanocarriers conjugated to TPP.