Journal
JOURNAL OF CONTROLLED RELEASE
Volume 291, Issue -, Pages 147-156Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2018.10.029
Keywords
Cell-penetrating peptides; Mitochondrial-targeting; Targeted drug delivery; Endosomal release; Chlorambucil
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The mitochondrial organelle is associated with many diseases, including diabetes, age-related neuro-degenerative diseases and cancer. Therefore, the effective delivery of drug molecules to mitochondria became increasingly important during the past years. Within this work, we designed and analyzed bifunctional hybrid peptides comprised of a mitochondrial targeting sequence (MTS) attached to a cell-penetrating peptide (CPP). Our results demonstrate that choice of the MTS must be carefully undertaken, since not every MTS that was selected was comparably capable to target mitochondria. In addition, we highlight the use of the CPP sC18 as necessary part of the hybrid construct, inducing not only cellular uptake, but likewise supporting sub-organelle uptake into the mitochondrial matrix. The herein designed cell-permeable mitochondrial targeting peptide was furthermore proven to enhance the intracellular uptake of the cytostatic drug chlorambucil, making it a powerful candidate for further studies in this important field.
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