Details
| Original language | English |
|---|---|
| Pages (from-to) | 17541-17551 |
| Number of pages | 11 |
| Journal | Chemistry - A European Journal |
| Volume | 20 |
| Issue number | 52 |
| Publication status | Published - 24 Oct 2014 |
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 alkynylor 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.
Keywords
- Antitumor agents, Hyperthermia, Maytansinoids, Mutasynthesis, Nanoparticles
ASJC Scopus subject areas
- Chemical Engineering(all)
- Catalysis
- Chemistry(all)
- Organic Chemistry
Sustainable Development Goals
Cite this
- Standard
- Harvard
- Apa
- Vancouver
- BibTeX
- RIS
In: Chemistry - A European Journal, Vol. 20, No. 52, 24.10.2014, p. 17541-17551.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Preparation of thermocleavable conjugates based on ansamitocin and superparamagnetic nanostructured particles by a chemobiosynthetic approach
AU - Mancuso, Lena
AU - Knobloch, Tobias
AU - Buchholz, Jessica
AU - Hartwig, Jan
AU - Möller, Lena
AU - Seidel, Katja
AU - Collisi, Wera
AU - Sasse, Florenz
AU - Kirschning, Andreas
PY - 2014/10/24
Y1 - 2014/10/24
N2 - 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 alkynylor 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.
AB - 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 alkynylor 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.
KW - Antitumor agents
KW - Hyperthermia
KW - Maytansinoids
KW - Mutasynthesis
KW - Nanoparticles
UR - http://www.scopus.com/inward/record.url?scp=84920154661&partnerID=8YFLogxK
U2 - 10.1002/chem.201404502
DO - 10.1002/chem.201404502
M3 - Article
C2 - 25418325
AN - SCOPUS:84920154661
VL - 20
SP - 17541
EP - 17551
JO - Chemistry - A European Journal
JF - Chemistry - A European Journal
SN - 0947-6539
IS - 52
ER -