Attenuation of Mouse Melanoma by A/C Magnetic Field after Delivery of Bi-Magnetic Nanoparticles by Neural Progenitor Cells

Abstract

Localized magnetic hyperthermia as a treatment modality for cancer has generated renewed interest, particularly if it can be targeted to the tumor site. We examined whether tumor-tropic neural progenitor cells (NPCs) could be utilized as cell delivery vehicles for achieving preferential accumulation of core/shell iron/iron oxide magnetic nanoparticles (MNPs) within a mouse model of melanoma. We developed aminosiloxane-porphyrin functionalized MNPs, evaluated cell viability and loading efficiency, and transplanted neural progenitor cells loaded with this cargo into mice with melanoma. NPCs were efficiently loaded with core/shell Fe/Fe 3 O 4 MNPs with minimal cytotoxicity; the MNPs accumulated as aggregates in the cytosol. The NPCs loaded with MNPs could travel to subcutaneous melanomas, and after A/C (alternating current) magnetic field (AMF) exposure, the targeted delivery of MNPs by the cells resulted in a measurable regression of the tumors. The tumor attenuation was significant (p<0.05) a short time (24 hours) after the last of three AMF exposures. Keywords nanotechnology; cell-based; targeted delivery; magnetic nanoparticles; magnetic hyperthermia; melanoma; neural progenitor cellsThe incidence and mortality rate of malignant melanoma continues to increase at an alarming rate worldwide.1 Disseminated melanoma is not curable using current clinical * Corresponding author: Deryl Troyer, Department of Anatomy and Physiology, 228 Coles Hall, Kansas State University, Manhattan, KS 66506, USA troyer@vet.ksu.edu,. ** Both of these authors contributed equally to this work. Supporting Information Available:Supplemental Figures S1 and S2 show a TEM image of MNPs and a photo of a hemacytometer grid with trypan blue-stained, MNP-loaded NPCs, respectively. The figures and accompanying legends are available This material is available free of charge via the Internet at http://pubs.acs.org. NIH Public AccessAuthor Manuscript ACS Nano. Author manuscript; available in PMC 2011 December 28. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript tools; traditional chemotherapy is ineffective due to inherent drug-resistant characteristics of the disease.2 , 3The pioneering studies of Gordon et al. demonstrated induced intracellular hyperthermia using dextran magnetite nanoparticles in a high frequency magnetic field (such as 500 kHz); the advantages of magnetic nanoparticles (MNPs), such as negligible or low toxicity, biocompatibility, injectability into the blood stream, and potential accumulation in the target tumor, make them prime candidates for hyperthermia applications.4 However, the specific absorption rates (SARs) of those early systems were low. It will be of great importance to achieve a high monodispersity of the magnetic nanoparticles, because only then can the A/ C-excitation be optimized to achieve very high specific absorption rates. Magnetic hyperthermia has recently garnered new interest as a cancer therapy because technological advances allow heat delivery to be more precisely contro...

Stem cell-based photodynamic therapy

“…The first attempt to use bioluminescence from NIH 3T3 murine 15 fibroblasts, which were transfected with firefly luciferase, was reported in 2003 by A. J. MacRobert and coworkers. 23 The cells were loaded with D-luciferin and the photosensitizer rose bengal featuring a quantum yield of singlet-oxygen sensitization of   =0.75±0.05 in aqueous media.…”

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“…In the search for new cancer treatment methods able to overcome the multi-drug resistance found in many cancer types, it will be 15 advantageous to try new approaches. Classic chemotherapy focuses on killing cells that are dividing rapidly.…”

“…It has also been demonstrated that certain bacteria (e.g. Clostridium and Bifidobacterium 13 ), viruses 14 , and 70 neural stem cells 15 , when administered systemically, are able to gain entry to and replicate selectively in tumours. In addition many tissue/tumour specific promoters have been cloned, allowing transgene expression specifically in tumour tissues.…”

“…27 Mouse neural stem cells (NSC) were 45 used because they are known to "home" to numerous solid tumours. 15 The pGLuc-basic-1 vector contains the "humanized" coding sequence for secreted Gaussia luciferase (gLuc), for use in mammalian cells. The medium containing gLuc secreted from the C17.2 cells was harvested at 24 hours and used to treat 50 B16F10 mouse melanoma cells that had been independently cultured and treated with the supernatant from the mouse neural stem cells.…”