title: Magnetic-Fe/Fe(3)O(4)-nanoparticle-bound SN38 as carboxylesterase-cleavable prodrug for the delivery to tumors within monocytes/macrophages.
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(3)O(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.
authors.affiliation: Kansas State University, Department of Chemistry, CBC 201, Manhattan, KS 66506.
authors.forename: Hongwang
authors.initials: H
authors.lastname: Wang
authors.forename: Tej B
authors.initials: TB
authors.lastname: Shrestha
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Basel
authors.forename: Raj Kumar
authors.initials: RK
authors.lastname: Dani
authors.forename: Gwi-Moon
authors.initials: GM
authors.lastname: Seo
authors.forename: Sivasai
authors.initials: S
authors.lastname: Balivada
authors.forename: Marla M
authors.initials: MM
authors.lastname: Pyle
authors.forename: Heidy
authors.initials: H
authors.lastname: Prock
authors.forename: Olga B
authors.initials: OB
authors.lastname: Koper
authors.forename: Prem S
authors.initials: PS
authors.lastname: Thapa
authors.forename: David
authors.initials: D
authors.lastname: Moore
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Viktor
authors.initials: V
authors.lastname: Chikan
authors.forename: Deryl L
authors.initials: DL
authors.lastname: Troyer
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Bossmann