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


Show simple item record Wang, Hongwang Shrestha, Tej B. Basel, Matthew T. Dani, Raj K. Seo, Gwi-Moon Balivada, Sivasai Pyle, Marla M. Prock, Heidy Koper, Olga B. Thapa, Prem S. Moore, David Li, Ping Chikan, Viktor Troyer, Deryl L. Bossmann, Stefan H. 2012-07-26T20:17:32Z 2012-07-26T20:17:32Z 2012-07-26
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 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 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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