Magnetic-Fe/Fe3O4-nanoparticle-bound SN38 as carboxylesterase-cleavable prodrug for the delivery to tumors within monocytes/macrophages

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dc.contributor.author Wang, Hongwang
dc.contributor.author Shrestha, Tej B.
dc.contributor.author Basel, Matthew T.
dc.contributor.author Dani, Raj K.
dc.contributor.author Seo, Gwi-Moon
dc.contributor.author Balivada, Sivasai
dc.contributor.author Pyle, Marla M.
dc.contributor.author Prock, Heidy
dc.contributor.author Koper, Olga B.
dc.contributor.author Thapa, Prem S.
dc.contributor.author Moore, David
dc.contributor.author Li, Ping
dc.contributor.author Chikan, Viktor
dc.contributor.author Troyer, Deryl L.
dc.contributor.author Bossmann, Stefan H.
dc.date.accessioned 2012-07-26T20:17:32Z
dc.date.available 2012-07-26T20:17:32Z
dc.date.issued 2012-07-26
dc.identifier.uri http://hdl.handle.net/2097/14093
dc.description.abstract The targeted delivery of therapeutics to the tumor site is highly desirable in cancer treatment, because it is capable of minimizing collateral damage. Herein, we report the synthesis of a nanoplatform, which is composed of a 15 ± 1 nm diameter core/shell Fe/Fe[subscript]3O[subscript]4 magnetic nanoparticles (MNPs) and the topoisomerase I blocker SN38 bound to the surface of the MNPs via a carboxylesterase cleavable linker. This nanoplatform demonstrated high heating ability (SAR = 522 ± 40 W/g) in an AC-magnetic field. For the purpose of targeted delivery, this nanoplatform was loaded into tumor-homing double-stable RAW264.7 cells (mouse monocyte/macrophage-like cells (Mo/Ma)), which have been engineered to express intracellular carboxylesterase (InCE) upon addition of doxycycline by a Tet-On Advanced system. The nanoplatform was taken up efficiently by these tumor-homing cells. They showed low toxicity even at high nanoplatform concentration. SN38 was released successfully by switching on the Tet-On Advanced system. We have demonstrated that this nanoplatform can be potentially used for thermochemotherapy. We will be able to achieve the following goals: (1) Specifically deliver the SN38 prodrug and magnetic nanoparticles to the cancer site as the payload of tumor-homing double-stable RAW264.7 cells; (2) Release of chemotherapeutic SN38 at the cancer site by means of the self-containing Tet-On Advanced system; (3) Provide localized magnetic hyperthermia to enhance the cancer treatment, both by killing cancer cells through magnetic heating and by activating the immune system. en_US
dc.relation.uri http://www.beilstein-journals.org/bjnano/single/articleFullText.htm?publicId=2190-4286-3-51 en_US
dc.subject Cell-based delivery en_US
dc.subject Chemotherapeutic prodrug en_US
dc.subject Magnetic Fe/Fe3O4 nanoparticles en_US
dc.subject SN38 en_US
dc.title Magnetic-Fe/Fe3O4-nanoparticle-bound SN38 as carboxylesterase-cleavable prodrug for the delivery to tumors within monocytes/macrophages en_US
dc.type Article (publisher version) en_US
dc.date.published 2012 en_US
dc.citation.doi doi:10.3762/bjnano.3.51 en_US
dc.citation.epage 455 en_US
dc.citation.jtitle Beilstein Journal of Nanotechnology en_US
dc.citation.spage 444 en_US
dc.citation.volume 3 en_US
dc.contributor.authoreid hongwang en_US
dc.contributor.authoreid tbs3 en_US
dc.contributor.authoreid mbasel en_US
dc.contributor.authoreid rdani en_US
dc.contributor.authoreid sbalivad en_US
dc.contributor.authoreid mpyle en_US
dc.contributor.authoreid hprock en_US
dc.contributor.authoreid pli en_US
dc.contributor.authoreid chikan en_US
dc.contributor.authoreid troyer en_US
dc.contributor.authoreid sbossman en_US

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