Peptide-Mediated Delivery of Chemical Probes and Therapeutics to Mitochondria

作者：Sae Rin Jean, Marya Ahmed, Eric K. Lei, Simon Wisnovsky, Shana O. Kelley · 发表于：Accounts of Chemical Research · 年份：2016 · DOI：10.1021/acs.accounts.6b00277 · 被引用次数：250 · 研究领域：RNA Interference and Gene Delivery、Advanced biosensing and bioanalysis techniques、ATP Synthase and ATPases Research

Mitochondria are organelles with critical roles in key processes within eukaryotic cells, and their dysfunction is linked with numerous diseases including neurodegenerative disorders and cancer. Pharmacological manipulation of mitochondrial function is therefore important both for basic science research and eventually, clinical medicine. However, in comparison to other organelles, mitochondria are difficult to access due to their hydrophobic and dense double membrane system as well as their negative membrane potential. To tackle the challenge of targeting these important subcellular compartments, significant effort has been put forward to develop mitochondria-targeted systems capable of transporting bioactive cargo into the mitochondrial interior. Systems now exist that utilize small molecule, peptide, liposome, and nanoparticle-based transport. The vectors available vary in size and structure and can facilitate transport of a variety of compounds for mitochondrial delivery. Notably, peptide-based delivery scaffolds offer attractive features such as ease of synthesis, tunability, biocompatibility, and high uptake both in cellulo and in vivo. Owing to their simple and modular synthesis, these peptides are highly adaptable for delivering chemically diverse cargo. Key design features of mitochondria-targeted peptides include cationic charge, which allows them to harness the negative membrane potential of mitochondria, and lipophilicity, which permits favorable interaction with h...