title: Targeted and controlled anticancer drug delivery and release with magnetoelectric nanoparticles.
abstract: It is a challenge to eradicate tumor cells while sparing normal cells. We used magnetoelectric nanoparticles (MENs) to control drug delivery and release. The physics is due to electric-field interactions (i) between MENs and a drug and (ii) between drug-loaded MENs and cells. MENs distinguish cancer cells from normal cells through the membrane's electric properties; cancer cells have a significantly smaller threshold field to induce electroporation. In vitro and in vivo studies (nude mice with SKOV-3 xenografts) showed that (i) drug (paclitaxel (PTX)) could be attached to MENs (30-nm CoFe2O4@BaTiO3 nanostructures) through surface functionalization to avoid its premature release, (ii) drug-loaded MENs could be delivered into cancer cells via application of a d.c. field (~100 Oe), and (iii) the drug could be released off MENs on demand via application of an a.c. field (~50 Oe, 100 Hz). The cell lysate content was measured with scanning probe microscopy and spectrophotometry. MENs and control ferromagnetic and polymer nanoparticles conjugated with HER2-neu antibodies, all loaded with PTX were weekly administrated intravenously. Only the mice treated with PTX-loaded MENs (15/200 μg) in a field for three months were completely cured, as confirmed through infrared imaging and post-euthanasia histology studies via energy-dispersive spectroscopy and immunohistochemistry.
authors.affiliation: Department of Cellular Biology and Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, USAFlorida 33199, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Rodzinski
authors.affiliation: Department of Cellular Biology and Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, USAFlorida 33199, USA.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Guduru
authors.affiliation: Electrical and Computer Engineering, University of California, Riverside, CA 92521, USA.|Cellular Nanomed Inc., Weston, FL 33331, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Liang
authors.affiliation: Department of Electrical and Computer Engineering, Florida International University, Miami, FL 33174, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Hadjikhani
authors.affiliation: Department of Cellular Biology and Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, USAFlorida 33199, USA.
authors.forename: Tiffanie
authors.initials: T
authors.lastname: Stewart
authors.affiliation: Department of Electrical and Computer Engineering, Florida International University, Miami, FL 33174, USA.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Stimphil
authors.affiliation: Department of Obstetrics and Gynecology, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida 33199, USA.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Runowicz
authors.affiliation: Department of Pathology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.|John T. Macdonald Foundation Biomedical Nanotechnology Institute, University of Miami, Miami, FL 33136, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Cote
authors.affiliation: Department of Pathology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
authors.forename: Norman
authors.initials: N
authors.lastname: Altman
authors.affiliation: Department of Pathology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.|John T. Macdonald Foundation Biomedical Nanotechnology Institute, University of Miami, Miami, FL 33136, USA.
authors.forename: Ram
authors.initials: R
authors.lastname: Datar
authors.affiliation: Department of Cellular Biology and Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, USAFlorida 33199, USA.|Department of Electrical and Computer Engineering, Florida International University, Miami, FL 33174, USA.
authors.forename: Sakhrat
authors.initials: S
authors.lastname: Khizroev
mesh_terms: D000818:Animals; D000906:Antibodies / Q000737:chemistry / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods*; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry / Q000378:metabolism; D007279:Injections, Subcutaneous; D060526:Magnetic Fields; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D059346:Magnets; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000473:pathology / Q000628:therapy*; D017239:Paclitaxel / Q000494:pharmacology*; D010316:Particle Size; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D000906:Antibodies; D000972:Antineoplastic Agents, Phytogenic; D018796:Immunoconjugates; D058185:Magnetite Nanoparticles; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human