ROS-Responsive N-Alkylaminoferrocenes for Cancer-Cell-Specific Targeting of Mitochondria.
Viktor ReshetnikovSteffen DaumChristina JankoWeronika KarawackaRainer TietzeChristoph AlexiouSolomiya ParyzhakTetiana DumychRostyslav BilyyPhilipp TripalBenjamin SchmidRalf PalmisanoAndriy MokhirPublished in: Angewandte Chemie (International ed. in English) (2018)
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.
Keyphrases
- reactive oxygen species
- cancer therapy
- cell death
- cell cycle arrest
- induced apoptosis
- high efficiency
- papillary thyroid
- drug delivery
- dna damage
- anti inflammatory
- single molecule
- oxidative stress
- squamous cell
- endoplasmic reticulum stress
- squamous cell carcinoma
- randomized controlled trial
- mass spectrometry
- radiation therapy
- endoplasmic reticulum
- childhood cancer
- young adults
- climate change
- risk assessment
- adverse drug
- cell proliferation