Model‐Based Nanoengineered Pharmacokinetics of Iron‐Doped Copper Oxide for Nanomedical Applications. Issue 5 (9th January 2020)

• Record Type: Journal Article
• Authors: Naatz, Hendrik; Manshian, Bella B.; Rios Luci, Carla; Tsikourkitoudi, Vasiliki; Deligiannakis, Yiannis; Birkenstock, Johannes; Pokhrel, Suman; Mädler, Lutz; Soenen, Stefaan J.
• Is Part Of: Angewandte Chemie international edition. Volume 59:Issue 5(2020)
• Page Start: 1828
• Page End: 1836
• Publication Date: 2020-01-09
• Subjects: controlled pharmacokinetics -- copper oxide -- nanomedicine -- nanoparticles -- structure–release models; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201912312
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: 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 Cu 2+ 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. Abstract : A pharmacokinetic model : Dissolution kinetics from iron‐doped copper oxide nanoparticles were modelled to establish structure–release relationships. With those finely tuned kinetics, a cancer treatment orthogonal to conventional chemotherapy was achieved both in vitro and in vivo. Immunization of all animals occurred, rendering them protected against tumor relapse, even upon re‐engraftment of tumor cells.