Magnetic-Fe/Fe 3 O 4 -nanoparticle-bound SN38 as carboxylesterase-cleavable prodrug for the delivery to tumors within monocytes/macrophages

• Published in: Beilstein journal of nanotechnology Vol. 3; pp. 444 - 455
• Main Authors: Wang, Hongwang, Shrestha, Tej B, Basel, Matthew T, Dani, Raj Kumar, 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
• Format: Journal Article
• Language: English
• Published: 13.06.2012
• ISSN: 2190-4286; 2190-4286
• DOI: 10.3762/bjnano.3.51

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.