maytansine and Fever

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.

Topics: Cell Line, Tumor; Cell Proliferation; Cycloaddition Reaction; Ferric Compounds; Fever; Humans; Magnetics; Maytansine; Molecular Structure; Nanostructures; Silicon Dioxide

Topics: Adolescent; Child; Child, Preschool; Drug Evaluation; Drug Resistance; Fever; Humans; Infant; Leukemia, Lymphoid; Maytansine; Oxazines