Locoregional cancer treatment with magnetic drug targeting.
The specific delivery of chemotherapeutic agents to their desired targets with a minimum of systemic side effects is an important, ongoing challenge of chemotherapy. One approach, developed in the past to address this problem, is the i.v. injection of magnetic particles [ferrofluids (FFs)] bound to anticancer agents that are then concentrated in the desired area (e.g., the tumor) by an external magnetic field. In the present study, we treated squamous cell carcinoma in rabbits with FFs bound to mitoxantrone (FF-MTX) that was concentrated with a magnetic field. Experimental VX-2 squamous cell carcinoma was implanted in the median portion of the hind limb of New Zealand White rabbits (n = 26). When the tumor had reached a volume of approximately 3500 mm3, FF-MTX was injected intraarterially (i.a.; femoral artery) or i.v. (ear vein), whereas an external magnetic field was focused on the tumor. FF-MTX i.a. application with the external magnetic field resulted in a significant (P < 0.05), complete, and permanent remission of the squamous cell carcinoma compared with the control group (no treatment) and the i.v. FF-MTX group, with no signs of toxicity. The intratumoral accumulation of FFs was visualized both histologically and by magnetic resonance imaging. Thus, our data show that i.a. application of FF-MTX is successful in treating experimental squamous cell carcinoma. This "magnetic drug targeting" offers a unique opportunity to treat malignant tumors locoregionally without systemic toxicity. Furthermore, it may be possible to use these magnetic particles as a "carrier system" for a variety of anticancer agents, e.g., radionuclides, cancer-specific antibodies, and genes.
Alexiou
C
C
Department of Otorhinolaryngology, Head and Neck Surgery, Klinikum rechts der Isar, Technical University of Munich, Germany. C.Alexiou@lrz.tu-muenchen.de
Arnold
W
W
Klein
R J
RJ
Parak
F G
FG
Hulin
P
P
Bergemann
C
C
Erhardt
W
W
Wagenpfeil
S
S
Lübbe
A S
AS
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D003102:Colloids / Q000008:administration & dosage / Q000493:pharmacokinetics; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics; D008279:Magnetic Resonance Imaging; D008280:Magnetics; D008942:Mitoxantrone / Q000008:administration & dosage / Q000493:pharmacokinetics; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D011817:Rabbits
D000970:Antineoplastic Agents; D003102:Colloids; D004337:Drug Carriers; D005290:Ferric Compounds; C000499:ferric oxide; C021024:ferric hydroxide; D008942:Mitoxantrone