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ROS‐Responsive N‐Alkylaminoferrocenes for Cancer‐Cell‐Specific Targeting of Mitochondria |
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| Authors: | Viktor Reshetnikov Steffen Daum Dr. Christina Janko Weronika Karawacka Dr. Rainer Tietze Prof. Dr. Christoph Alexiou Dr. Solomiya Paryzhak Dr. Tetiana Dumych Prof. Dr. Rostyslav Bilyy Dr. Philipp Tripal Dr. Benjamin Schmid Dr. Ralf Palmisano Prof. Dr. Andriy Mokhir |
| Affiliation: | 1. Friedrich-Alexander-University of Erlangen-Nürnberg, Department of Chemistry and Pharmacy, Organic Chemistry Chair II, Erlangen, Germany;2. Department of Otorhinolaryngology, Head and Neck Surgery, Section of Experimental Oncology and Nanomedicine (SEON), Universit?tsklinikum Erlangen, Erlangen, Germany;3. Danylo Halytsky Lviv National Medical University, Lviv, Ukraine;4. Optical Imaging Centre Erlangen OICE, Friedrich-Alexander-University of Erlangen-Nürnberg, Erlangen, Germany |
| Abstract: | Mitochondrial membrane potential is more negative in cancer cells than in normal cells, allowing cancer targeting by delocalized lipophilic cations (DLCs). However, as the difference is rather small, these drugs affect also normal cells. Now a concept of pro‐DLCs is proposed based on an N‐alkylaminoferrocene structure. These prodrugs are activated by the reaction with reactive oxygen species (ROS) forming ferrocenium‐based DLCs. Since ROS are overproduced in cancer, the high‐efficiency cancer‐cell‐specific targeting of mitochondria could be achieved as demonstrated by fluorescence microscopy in combination with two fluorogenic pro‐DLCs in vitro and in vivo. We prepared a conjugate of another pro‐DLC with a clinically approved drug carboplatin and confirmed that its accumulation in mitochondria was higher than that of the free drug. This was reflected in the substantially higher anticancer effect of the conjugate. |
| Keywords: | aminoferrocene anticancer prodrugs cancer mitochondria targeting reactive oxygen species |