PMID- 23016149 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20120928 LR - 20211021 IS - 2190-4286 (Electronic) IS - 2190-4286 (Linking) VI - 3 DP - 2012 TI - Magnetic-Fe/Fe(3)O(4)-nanoparticle-bound SN38 as carboxylesterase-cleavable prodrug for the delivery to tumors within monocytes/macrophages. PG - 444-55 AB - 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. FAU - Wang, Hongwang AU - Wang H AD - Kansas State University, Department of Chemistry, CBC 201, Manhattan, KS 66506. FAU - Shrestha, Tej B AU - Shrestha TB FAU - Basel, Matthew T AU - Basel MT FAU - Dani, Raj Kumar AU - Dani RK FAU - Seo, Gwi-Moon AU - Seo GM FAU - Balivada, Sivasai AU - Balivada S FAU - Pyle, Marla M AU - Pyle MM FAU - Prock, Heidy AU - Prock H FAU - Koper, Olga B AU - Koper OB FAU - Thapa, Prem S AU - Thapa PS FAU - Moore, David AU - Moore D FAU - Li, Ping AU - Li P FAU - Chikan, Viktor AU - Chikan V FAU - Troyer, Deryl L AU - Troyer DL FAU - Bossmann, Stefan H AU - Bossmann SH LA - eng PT - Journal Article DEP - 20120613 PL - Germany TA - Beilstein J Nanotechnol JT - Beilstein journal of nanotechnology JID - 101551563 PMC - PMC3388369 OTO - NOTNLM OT - SN38 OT - cell-based delivery OT - chemotherapeutic prodrug OT - magnetic Fe/Fe3O4 nanoparticles EDAT- 2012/09/28 06:00 MHDA- 2012/09/28 06:01 PMCR- 2012/06/13 CRDT- 2012/09/28 06:00 PHST- 2012/03/30 00:00 [received] PHST- 2012/05/24 00:00 [accepted] PHST- 2012/09/28 06:00 [entrez] PHST- 2012/09/28 06:00 [pubmed] PHST- 2012/09/28 06:01 [medline] PHST- 2012/06/13 00:00 [pmc-release] AID - 10.3762/bjnano.3.51 [doi] PST - ppublish SO - Beilstein J Nanotechnol. 2012;3:444-55. doi: 10.3762/bjnano.3.51. Epub 2012 Jun 13.