Magnetic Nanoparticle-Based Dianthin Targeting for Controlled Drug Release Using the Endosomal Escape Enhancer SO1861
Ajmal Zarinwall,
Mazdak Asadian-Birjand,
Didem Ag Seleci,
Viktor Maurer,
Alexandra Trautner,
Georg Garnweitner,
Hendrik Fuchs
Affiliations
Ajmal Zarinwall
Institute for Particle Technology (iPAT), Technische Universität Braunschweig, 38104 Braunschweig, Germany
Mazdak Asadian-Birjand
Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, 13353 Berlin, Germany
Didem Ag Seleci
Institute for Particle Technology (iPAT), Technische Universität Braunschweig, 38104 Braunschweig, Germany
Viktor Maurer
Institute for Particle Technology (iPAT), Technische Universität Braunschweig, 38104 Braunschweig, Germany
Alexandra Trautner
Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, 13353 Berlin, Germany
Georg Garnweitner
Institute for Particle Technology (iPAT), Technische Universität Braunschweig, 38104 Braunschweig, Germany
Hendrik Fuchs
Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, 13353 Berlin, Germany
Targeted tumor therapy can provide the basis for the inhibition of tumor growth. However, a number of toxin-based therapeutics lack efficacy because of insufficient endosomal escape after being internalized by endocytosis. To address this problem, the potential of glycosylated triterpenoids, such as SO1861, as endosomal escape enhancers (EEE) for superparamagnetic iron oxide nanoparticle (SPION)-based toxin therapy was investigated. Herein, two different SPION-based particle systems were synthesized, each selectively functionalized with either the targeted toxin, dianthin-epidermal growth factor (DiaEGF), or the EEE, SO1861. After applying both particle systems in vitro, an almost 2000-fold enhancement in tumor cell cytotoxicity compared to the monotherapy with SPION-DiaEGF and a 6.7-fold gain in specificity was observed. Thus, the required dose of the formulation was appreciably reduced, and the therapeutic window widened.
