M. Sc. Hendrik Naatz, Dr. Bella B. Manshian, Dr. Carla Rios Luci, Dr. Vasiliki Tsikourkitoudi, Prof. Dr. Yiannis Deligiannakis, Dr. Johannes Birkenstock, Dr. Suman Pokhrel, Prof. Dr. Lutz Mädler, Dr. Stefaan J. Soenen
Angewandte Chemie - International Edition (2020) 59, 1828-1836
The progress in nanomedicine (NM) using nanoparticles (NPs) is mainly based on drug carriers for the delivery of classical chemotherapeutics. As low NM delivery rates limit therapeutic efficacy, an entirely different approach was investigated. A homologous series of engineered CuO NPs was designed for dual purposes (carrier and drug) with a direct chemical composition–biological functionality relationship. Model-based dissolution kinetics of CuO NPs in the cellular interior at post-exposure conditions were controlled through Fe-doping for intra/extra cellular Cu2+ and biological outcome. Through controlled ion release and reactions taking place in the cellular interior, tumors could be treated selectively, in vitro and in vivo. Locally administered NPs enabled tumor cells apoptosis and stimulated systemic anti-cancer immune responses. We clearly show therapeutic effects without tumor cells relapse post-treatment with 6 % Fe-doped CuO NPs combined with myeloid-derived suppressor cell silencing.