ROS-Responsive N-Alkylaminoferrocenes for Cancer-Cell-Specific Targeting of Mitochondria

Reshetnikov V, Daum S, Janko C, Karawacka W, Tietze R, Alexiou C, Paryzhak S, Dumych T, Bilyy R, Tripal P, Schmid B, Palmisano R, Mokhir A (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Angewandte Chemie International Edition Wiley

Book Volume: 57

Pages Range: 11943-11946

Journal Issue: 37

DOI: 10.1002/anie.201805955

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.

Authors with CRIS profile

Viktor Reshetnikov Lehrstuhl für Organische Chemie II Steffen Daum Lehrstuhl für Organische Chemie II Christina Janko Department of Otorhinolaryngology – Head and Neck Surgery Rainer Tietze Department of Otorhinolaryngology – Head and Neck Surgery Christoph Alexiou Professur für Nanomedizin Philipp Tripal Optical Imaging Center Erlangen (OICE) Benjamin Schmid Optical Imaging Center Erlangen (OICE) Ralf Palmisano Optical Imaging Center Erlangen (OICE) Andriy Mokhir Professur für Organische Chemie

Involved external institutions

Danylo Halytsky Lviv National Medical University / Львiвський Національний Медичний Унiверситет iм. Данила Галицького UA Ukraine (UA)

How to cite

APA:

Reshetnikov, V., Daum, S., Janko, C., Karawacka, W., Tietze, R., Alexiou, C.,... Mokhir, A. (2018). ROS-Responsive N-Alkylaminoferrocenes for Cancer-Cell-Specific Targeting of Mitochondria. Angewandte Chemie International Edition, 57(37), 11943-11946. https://dx.doi.org/10.1002/anie.201805955

MLA:

Reshetnikov, Viktor, et al. "ROS-Responsive N-Alkylaminoferrocenes for Cancer-Cell-Specific Targeting of Mitochondria." Angewandte Chemie International Edition 57.37 (2018): 11943-11946.

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