title: External magnet improves antitumor effect of vinblastine and the suppression of metastasis.
abstract: The use of magnetic drug targeting (MDT) to selectively deliver chemotherapeutic drugs to tumor cells is a widely investigated approach; however, the notion of targeting tumor endothelial cells by this method is a fairly new concept. Positively-charged (cationic) liposomes have an extraordinarily high affinity for tumor vessels, but heterogeneous targeting is frequently observed. In order to improve on the overall efficiency of targeting tumor vessels, we investigated the use of an externally applied magnetic field together with magnetic cationic liposomes (MCLs) for cancer treatment. We examined the antitumor effect of the chemotherapeutic agent vinblastine loaded in MCLs, using a murine model of melanoma. Two hours following i.v. administration of MCLs, we observed significant tumor vascular uptake with use of an external magnet (15.9 +/- 6.3%) compared to no magnet (5 +/- 1.3%). The administration of vinblastine-loaded MCLs with the magnet produced a significant antitumor effect, reducing the presence of tumor nodules in preferential sites of metastasis compared to untreated and free drug control groups. CD31 immunostaining revealed a decrease in the general length of tumor blood vessels, altered vascular morphology and interruptions in the tumor vascular lining for the vinblastine-loaded MCL groups. Drug-loaded MCLs with magnetic fields may represent a promising combination approach for cancer treatment.
authors.affiliation: Department of Pharmaceutical Sciences, Bouvé College of Health Sciences, Northeastern University, Boston, Massachusetts, USA.
authors.forename: Suman
authors.initials: S
authors.lastname: Dandamudi
authors.forename: Vishwesh
authors.initials: V
authors.lastname: Patil
authors.forename: William
authors.initials: W
authors.lastname: Fowle
authors.forename: Ban-An
authors.initials: BA
authors.lastname: Khaw
authors.forename: Robert B
authors.initials: RB
authors.lastname: Campbell
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002412:Cations / Q000494:pharmacology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D007150:Immunohistochemistry; D008081:Liposomes / Q000494:pharmacology; D008280:Magnetics; D008546:Melanoma, Experimental / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology / Q000648:ultrastructure; D051379:Mice; D016513:Mice, SCID; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000648:ultrastructure; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D013997:Time Factors; D047368:Tumor Burden; D014747:Vinblastine / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002412:Cations; D008081:Liposomes; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D014747:Vinblastine