Differences in uptake, localization, and processing of PNAs modified by COX VIII pre-sequence peptide and by triphenylphoshonium cation into mitochondria of tumor cells

作者：Lamla Markus; Seliger Hartmut; Kaufmann Dieter^*

来源：Drug Delivery, 2010, 17(4): 263-271.

DOI：10.3109/10717541003702777

• Peptide nucleic acids
• mtDNA
• delivery
• TPP-PNA
• peptide-PNA

Two approaches to target PNAs (peptide nucleic acids) into mitochondria of HeLa cells were compared. In the first, PNA was modified with the lipophilic cation TPP. TPP-PNA accumulated rapidly within mitochondria driven by the membrane potential. It was found to be associated mainly with the mitochondrial membranes. In the second approach the COX VIII pre-sequence peptide was added to the PNA resulting in slow uptake of the peptide-PNA into the mitochondrial matrix. Whereas the amount of the uptake was lower, peptide-PNA was processed intramitochondrially in contrast to the TPP-PNA. Using the Chariot system to cross the cell membrane of HeLa cells, the uptake of peptide-PNA into the mitochondria was demonstrated. If a matrix localization of the free PNA is a pre-requisite for the PNA interaction with mitochondrial DNA, the coupling PNA with an appropriate peptide seems to be the better strategy.</.

• 出版日期2010-5