A Bio-Chemosynthetic Approach to Superparamagnetic Iron Oxide-Ansamitocin Conjugates for Use in Magnetic Drug Targeting
- Resource Type
- Authors
- Andreas Kirschning; Nadja-Carola Bigall; Jan F. Miethe; Yu Xie; Asha Balakrishnan; Michael Ott; Katja Seidel; Liang-Liang Wang; David A. Candito
- Source
- Chemistry (Weinheim an der Bergstrasse, Germany). 23(10)
- Subject
- Cell Survival
Iron oxide
Nanotechnology
010402 general chemistry
01 natural sciences
Ferric Compounds
Catalysis
chemistry.chemical_compound
Mice
Biosynthesis
Cell Line, Tumor
Hydroxybenzoates
Animals
Maytansine
Thermolabile
Magnetite Nanoparticles
Cycloaddition Reaction
010405 organic chemistry
Organic Chemistry
General Chemistry
Semisynthesis
Combinatorial chemistry
0104 chemical sciences
Stille reaction
chemistry
Targeted drug delivery
Linker
Conjugate
- Language
- ISSN
- 1521-3765
A combination of mutasynthesis using a mutant strain of A. pretiosum blocked in the biosynthesis of amino-hydroxybenzoic acid (AHBA) and semisynthesis relying on a Stille cross-coupling step provided access to new ansamitocin derivatives of which one was attached by a thermolabile linker to nanostructured iron oxide particles. When exposed to an oscillating electromagnetic field the resulting iron oxide/ansamitocin conjugate 19 heats up in an aqueous suspension and the ansamitocin derivative 16 is released by means of a retro-Diels-Alder reaction. It exerts strong antiproliferative activity (IC50 =4.8 ng mg-1 ) in mouse fibroblasts. These new types of conjugates have the potential for combating cancer through hyperthermia and chemotherapy using an electromagnetic external trigger.