TY - JOUR

T1 - Synthesis of Magnetic-Nanoparticle/Ansamitocin Conjugates

T2 - Inductive Heating Leads to Decreased Cell Proliferation In Vitro and Attenuation Of Tumour Growth In Vivo

AU - Seidel, Katja

AU - Balakrishnan, Asha

AU - Alexiou, Christoph

AU - Janko, Christina

AU - Komoll, Ronja Melinda

AU - Wang, Liangliang

AU - Kirschning, Andreas

AU - Ott, Michael

N1 - Funding information: The work was funded by the Deutsche Forschungsgemeinschaft (Cluster of Excellence REBIRTH; “From Regenerative Biology to Reconstructive Therapy” EXC 62, the Cluster of Excellence EAM; “Engineering of Advanced Materials” EXC 315 and AL 552/8-1), the Ministry of Science and Culture of Lower Saxony (MWK; graduate school HSN) and the Bavarian State Ministry for the Environment and Consumer Protection. We thank H. Herzog and Prof. S. Katusic (EVONIK Industries, AG, Essen, Germany) for technical advice. We are grateful to N. C. Bigall and J. F. Miethe (institute of physical chemistry, Leibniz University Hannover) for carrying out transmission electron microscopy measurements (TEM) (see Supporting Information). Animal experiments have been approved by local authorities under AZ 33.19-42502-04-14/1662 (Niedersächsiches Landesamt für Verbraucherschutz und Lebensmittelsicherheit). The work was funded by the Deutsche Forschungsgemeinschaft (Cluster of Excellence REBIRTH; ?From Regenerative Biology to Reconstructive Therapy? EXC 62, the Cluster of Excellence EAM; ?Engineering of Advanced Materials? EXC 315 and AL 552/8-1), the Ministry of Science and Culture of Lower Saxony (MWK; graduate school HSN) and the Bavarian State Ministry for the Environment and Consumer Protection. We thank H. Herzog and Prof. S. Katusic (EVONIK Industries, AG, Essen, Germany) for technical advice. We are grateful to N. C. Bigall and J. F. Miethe (institute of physical chemistry, Leibniz University Hannover) for carrying out transmission electron microscopy measurements (TEM) (see Supporting Information). Animal experiments have been approved by local authorities under AZ 33.19-42502-04-14/1662 (Nieders?chsiches Landesamt f?r Verbraucherschutz und Lebensmittelsicherheit).

PY - 2017/9/7

Y1 - 2017/9/7

N2 - Conjugates based on nanostructured, superparamagnetic particles, a thermolabile linker and a cytotoxic maytansinoid were developed to serve as a model for tumour-selective drug delivery and release. It combines chemo- with thermal therapy. The linker-modified toxin was prepared by a combination of biotechnology and semisynthesis. Drug release was achieved by hyperthermia through an external oscillating electromagnetic field that induces heat inside the particles. Efficacy of this release concept was demonstrated both for cancer cell proliferation in vitro, and for tumour growth in vivo, in a xenograft mouse model. Biocompatibility studies for these magnetic-nanoparticle/ansamitocin conjugates complement this work.

AB - Conjugates based on nanostructured, superparamagnetic particles, a thermolabile linker and a cytotoxic maytansinoid were developed to serve as a model for tumour-selective drug delivery and release. It combines chemo- with thermal therapy. The linker-modified toxin was prepared by a combination of biotechnology and semisynthesis. Drug release was achieved by hyperthermia through an external oscillating electromagnetic field that induces heat inside the particles. Efficacy of this release concept was demonstrated both for cancer cell proliferation in vitro, and for tumour growth in vivo, in a xenograft mouse model. Biocompatibility studies for these magnetic-nanoparticle/ansamitocin conjugates complement this work.

KW - antitumour agents

KW - biotransformations

KW - in vivo studies

KW - iron

KW - maytansin

KW - nanoparticles

UR - http://www.scopus.com/inward/record.url?scp=85026473793&partnerID=8YFLogxK

U2 - 10.1002/chem.201701491

DO - 10.1002/chem.201701491

M3 - Article

C2 - 28585348

AN - SCOPUS:85026473793

VL - 23

SP - 12326

EP - 12337

JO - Chemistry - A European Journal

JF - Chemistry - A European Journal

SN - 0947-6539

IS - 50

ER -