Targeted and controlled anticancer drug delivery and release with magnetoelectric nanoparticles

Alexandra Rodzinski; Rakesh Guduru; Ping Liang; Ali Hadjikhani; Tiffanie Stewart; Emmanuel Stimphil; Carolyn Runowicz; Richard Cote; Norman Altman; Ram Datar; Sakhrat Khizroev

doi:10.1038/srep20867

Targeted and controlled anticancer drug delivery and release with magnetoelectric nanoparticles

Alexandra Rodzinski, Rakesh Guduru, Ping Liang, Ali Hadjikhani, Tiffanie Stewart, Emmanuel Stimphil, Carolyn Runowicz, Richard Cote, Norman Altman, Ram Datar, Sakhrat Khizroev

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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.

Original language	English
Article number	20867
Journal	Scientific reports
Volume	6
DOIs	https://doi.org/10.1038/srep20867
State	Published - Feb 15 2016

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@article{0057e65cd7ea435bbc57fd28a9ff56a1,

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.",

author = "Alexandra Rodzinski and Rakesh Guduru and Ping Liang and Ali Hadjikhani and Tiffanie Stewart and Emmanuel Stimphil and Carolyn Runowicz and Richard Cote and Norman Altman and Ram Datar and Sakhrat Khizroev",

note = "Funding Information: We acknowledge partial financial support from National Science Foundation (NSF) awards # ECCS-1408063 (SK) and IIP-1237818 (SK), National Institute of Health (NIH) DA # R01DA034547-01 (SK) and NIGMS R25 GM061347 (ES), and Neuroscience Centers of Florida Foundation (NSCFF) (SK). We thank Dr. Seza Gulec for many insightful and inspiring discussions on cancer research. We thank Dr. Jeremy Chambers for his invaluable advice on IR imaging, Dr. Horatiu Venerian for his continuous support during animal studies, Dr. Erasmo Perera for preparation of biological tissues and help with immunohistochemistry analysis, and Graduate Student Athulya Mohanan Sureshkumari and Medical Student Mohamad El Churafa for help with H&E imaging.",

year = "2016",

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day = "15",

doi = "10.1038/srep20867",

language = "English",

volume = "6",

journal = "Scientific reports",

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T1 - Targeted and controlled anticancer drug delivery and release with magnetoelectric nanoparticles

AU - Rodzinski, Alexandra

AU - Guduru, Rakesh

AU - Liang, Ping

AU - Hadjikhani, Ali

AU - Stewart, Tiffanie

AU - Stimphil, Emmanuel

AU - Runowicz, Carolyn

AU - Cote, Richard

AU - Altman, Norman

AU - Datar, Ram

AU - Khizroev, Sakhrat

N1 - Funding Information: We acknowledge partial financial support from National Science Foundation (NSF) awards # ECCS-1408063 (SK) and IIP-1237818 (SK), National Institute of Health (NIH) DA # R01DA034547-01 (SK) and NIGMS R25 GM061347 (ES), and Neuroscience Centers of Florida Foundation (NSCFF) (SK). We thank Dr. Seza Gulec for many insightful and inspiring discussions on cancer research. We thank Dr. Jeremy Chambers for his invaluable advice on IR imaging, Dr. Horatiu Venerian for his continuous support during animal studies, Dr. Erasmo Perera for preparation of biological tissues and help with immunohistochemistry analysis, and Graduate Student Athulya Mohanan Sureshkumari and Medical Student Mohamad El Churafa for help with H&E imaging.

PY - 2016/2/15

Y1 - 2016/2/15

N2 - 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.

AB - 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.

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U2 - 10.1038/srep20867

DO - 10.1038/srep20867

M3 - Article

C2 - 26875783

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SN - 2045-2322

VL - 6

JO - Scientific reports

JF - Scientific reports

M1 - 20867

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Targeted and controlled anticancer drug delivery and release with magnetoelectric nanoparticles

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