Targeted and controlled anticancer drug delivery and release with magnetoelectric nanoparticles

Sci Rep. 2016 Feb 15:6:20867. doi: 10.1038/srep20867.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibodies / chemistry
  • Antibodies / metabolism
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Cell Line, Tumor
  • Drug Delivery Systems / instrumentation
  • Drug Delivery Systems / methods*
  • Female
  • Humans
  • Immunoconjugates / chemistry
  • Immunoconjugates / metabolism
  • Injections, Subcutaneous
  • Magnetic Fields
  • Magnetite Nanoparticles / chemistry*
  • Magnetite Nanoparticles / ultrastructure
  • Magnets
  • Mice
  • Mice, Nude
  • Ovarian Neoplasms / pathology
  • Ovarian Neoplasms / therapy*
  • Paclitaxel / pharmacology*
  • Particle Size
  • Receptor, ErbB-2 / chemistry
  • Receptor, ErbB-2 / metabolism
  • Treatment Outcome
  • Xenograft Model Antitumor Assays

Substances

  • Antibodies
  • Antineoplastic Agents, Phytogenic
  • Immunoconjugates
  • Magnetite Nanoparticles
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Paclitaxel