title: Inhalable magnetic nanoparticles for targeted hyperthermia in lung cancer therapy.
abstract: Lung cancer (specifically, non-small cell lung cancer; NSCLC) is the leading cause of cancer-related deaths in the United States. Poor response rates and survival with current treatments clearly indicate the urgent need for developing an effective means to treat NSCLC. Magnetic hyperthermia is a non-invasive approach for tumor ablation, and is based on heat generation by magnetic materials, such as superparamagnetic iron oxide (SPIO) nanoparticles, when subjected to an alternating magnetic field. However, inadequate delivery of magnetic nanoparticles to tumor cells can result in sub-lethal temperature change and induce resistance while non-targeted delivery of these particles to the healthy tissues can result in toxicity. In our studies, we evaluated the effectiveness of tumor-targeted SPIO nanoparticles for magnetic hyperthermia of lung cancer. EGFR-targeted, inhalable SPIO nanoparticles were synthesized and characterized for targeting lung tumor cells as well as for magnetic hyperthermia-mediated antitumor efficacy in a mouse orthotopic model of NSCLC. Our results show that EGFR targeting enhances tumor retention of SPIO nanoparticles. Further, magnetic hyperthermia treatment using targeted SPIO nanoparticles resulted in significant inhibition of in vivo lung tumor growth. Overall, this work demonstrates the potential for developing an effective anticancer treatment modality for the treatment of NSCLC based on targeted magnetic hyperthermia.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, United States.
authors.forename: Tanmoy
authors.initials: T
authors.lastname: Sadhukha
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Wiedmann
authors.forename: Jayanth
authors.initials: J
authors.lastname: Panyam
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000628:therapy*; D016923:Cell Death; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004705:Endocytosis; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D006979:Hyperthermia, Induced; D007322:Instillation, Drug; D007501:Iron / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000473:pathology / Q000628:therapy*; D058185:Magnetite Nanoparticles / Q000008:administration & dosage* / Q000627:therapeutic use*; D051379:Mice; D014018:Tissue Distribution
chemical_list: D058185:Magnetite Nanoparticles; D007501:Iron; D066246:ErbB Receptors