title: Preparation of thermocleavable conjugates based on ansamitocin and superparamagnetic nanostructured particles by a chemobiosynthetic approach.
abstract: A combination of mutasynthesis, precursor-directed biosynthesis and semisynthesis provides access to new ansamitocin derivatives including new nanostructured particle-drug conjugates. These conjugates are based on the toxin ansamitocin and superparamagnetic iron oxide-silica core shell particles. New ansamitocin derivatives that are functionalized either with alkynyl- or azido groups in the ester side chain at C-3 are attached to nanostructured iron oxide core-silica shell particles. Upon exposure to an oscillating electromagnetic field these conjugates heat up and the ansamitocin derivatives are released by a retro-Diels-Alder reaction. For example, one ansamitocin derivative exerts strong antiproliferative activity against various cancer cell lines in the lower nanomolar range while the corresponding nanostructured particle-drug conjugate is not toxic. Therefore, these new conjugates can serve as dormant toxins that can be employed simultaneously in hyperthermia and chemotherapy when external inductive heating is applied.
authors.affiliation: Institut für Organische Chemie und Biomolekulares Wirkstoffzentrum, Leibniz Universität Hannover, Schneiderberg 1B, 30167 Hannover (Germany).
authors.forename: Lena
authors.initials: L
authors.lastname: Mancuso
authors.forename: Tobias
authors.initials: T
authors.lastname: Knobloch
authors.forename: Jessica
authors.initials: J
authors.lastname: Buchholz
authors.forename: Jan
authors.initials: J
authors.lastname: Hartwig
authors.forename: Lena
authors.initials: L
authors.lastname: Möller
authors.forename: Katja
authors.initials: K
authors.lastname: Seidel
authors.forename: Wera
authors.initials: W
authors.lastname: Collisi
authors.forename: Florenz
authors.initials: F
authors.lastname: Sasse
authors.forename: Andreas
authors.initials: A
authors.lastname: Kirschning
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D061565:Cycloaddition Reaction; D005290:Ferric Compounds / Q000737:chemistry*; D005334:Fever / Q000139:chemically induced; D006801:Humans; D008280:Magnetics; D008453:Maytansine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000737:chemistry; D015394:Molecular Structure; D049329:Nanostructures / Q000737:chemistry*; D012822:Silicon Dioxide / Q000737:chemistry*
chemical_list: D005290:Ferric Compounds; D008453:Maytansine; C000499:ferric oxide; C015682:ansamitocins; D012822:Silicon Dioxide
keywords: antitumor agents; hyperthermia; maytansinoids; mutasynthesis; nanoparticles