Local moderate magnetically induced hyperthermia using an implant formed in situ in a mouse tumor model.
OBJECTIVE
We investigate a new heat delivery technique for the local treatment of solid tumors. The technique involves injecting a formulation that solidifies to form an implant in situ. This implant entraps superparamagnetic iron oxide nanoparticles (SPIONs) embedded in silica microbeads for magnetically induced moderate hyperthermia. Particle entrapment prevents phagocytosis and distant migration of SPIONs. The implant can be repeatedly heated by magnetic induction.


METHODS
We evaluated heating and treatment efficacies by means of thermometry and survival studies in nude mice carrying subcutaneous human colocarcinomas. At day 1, we injected the formulation into the tumor. At day 2, a single 20-min hyperthermia treatment was delivered by 141-kHz magnetic induction using field strengths of 9 to 12 mT under thermometry.


RESULTS
SPIONs embedded in silica microbeads were effectively confined within the implant at the injection site. Heat-induced necro-apoptosis was assessed by histology on day 3. On average, 12 mT resulted in tumor temperature of 47.8 degrees C, and over 70% tumor necrosis that correlated to the heat dose (AUC = 282 degrees C.min). In contrast, a 9-mT field strength induced tumoral temperature of 40 degrees C (AUC = 131 degrees C.min) without morphologically identifiable necrosis. Survival after treatment with 10.5 or 12 mT fields was significantly improved compared to non-implanted and implanted controls. Median survival times were 27 and 37 days versus 12 and 21 days respectively.


CONCLUSIONS
Five of eleven mice (45%) of the 12 mT group survived one year without any tumor recurrence, holding promise for tumor therapy using magnetically induced moderate hyperthermia through injectable implants.
School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva. Pol-edern.lerenard@unige.ch
Pol-Edern
PE
Le Renard
Franz
F
Buchegger
Alke
A
Petri-Fink
Frederik
F
Bosman
Daniel
D
Rüfenacht
Heinrich
H
Hofmann
Eric
E
Doelker
Olivier
O
Jordan
D000818:Animals; D017209:Apoptosis; D003110:Colonic Neoplasms / Q000628:therapy; D003911:Dextrans; D005240:Feasibility Studies; D005260:Female; D052203:Ferrosoferric Oxide; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D020007:Implants, Experimental; D007501:Iron / Q000008:administration & dosage*; D008280:Magnetics; D058185:Magnetite Nanoparticles; D051379:Mice; D008819:Mice, Nude; D008863:Microspheres; D053758:Nanoparticles; D009368:Neoplasm Transplantation; D010087:Oxides / Q000008:administration & dosage*; D012822:Silicon Dioxide
D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; D012822:Silicon Dioxide; D007501:Iron; C065507:ferumoxides; D052203:Ferrosoferric Oxide