Finding the best magnetic nanoparticle for hyperthermia treatment

Introduction

Magnetic fluid hyperthermia (MFH) is a noninvasive treatment that destroys cancer cells by heating a ferrofluid-impregnated malignant tissue with an AC magnetic field while causing minimal damage to the surrounding healthy tissue. The strength of the magnetic field must be sufficient to induce hyperthermia, but it is also limited by the human ability to safely withstand it. The ferrofluid material used for hyperthermia should be one that is readily produced and is nontoxic while providing sufficient heating. We examine six materials that have been considered as candidates for MFH use. Examining the heating produced by nanoparticles of these materials, barium ferrite and cobalt ferrite are unable to produce sufficient MFH heating, that from iron-cobalt occurs at a far too rapid rate to be safe, while fcc iron-platinum, magnetite and maghemite are all capable of producing stable controlled heating. We simulate the heating of ferrofluid-loaded tumors containing nanoparticles of the latter three materials to determine their effects on tumor tissue. These materials are viable MFH candidates since they can produce significant heating at the tumor center yet maintain the surrounding healthy tissue interface at a relatively safe temperature.

Cancer is a leading cause of human deaths [56,57]. Current treatments, such as surgery and chemotherapy, can have undesirable side effects, including harm to the surrounding healthy tissue. Hyperthermia is an alternative treatment that can destroy cancerous cells by significantly elevating the temperature of tumor cells while keeping that of the surrounding healthy tissue at a reasonable level [32]. One method to induce hyperthermia is by use of ferrofluids, which are colloidal suspensions of magnetic nanoparticles in a nonpolar medium. These fluids can be magnetically targeted to cancerous tissue after intravenous application [56]. The magnetic particles extravasate into the tumor due to the high microvascular permeability and interstitial diffusion in neoplastic tissue [58]. Thereafter, the magnetic nanoparticles are heated by exposing the tumor to a high frequency alternating magnetic field, causing thermonecrosis of the embedding tissue. This process is called magnetic fluid hyperthermia (MFH) [12,40,44,56,59,60].

In order to examine the potential of hyperthermia as a viable alternative to chemotherapy and radioactive treatment, it is necessary to define what such a treatment would hope to accomplish. Temperatures in the range of 41-45 C are enough to slow or halt the growth of cancerous tissue, but such heating can also damage healthy cells [32]. Thus, an ideal hyperthermia treatment should sufficiently increase the temperature of the tumor cells while maintaining the healthy tissue temperature below 41 C. Ferrofluid-based thermotherapy can be also accomplished through thermoablation, which typically heats tissues up to 56 C to cause their necrosis, coagulation, or carbonization by exposure to a noninvasive radio frequency AC magnetic field [12]. Local heat transfer from the nanoparticles increases the tissue temperature and ruptures the cell membranes [49,61].

Iron oxide nanoparticles such as magnetite, or its oxidized form maghemite, are the most biocompatible agents for MFH [44]. These particles are typically coated with a biocompatible polymer to prevent their aggregation and biodegradation for in vivo applications. Platinum and nickel are also magnetic nanoparticles, but are toxic and vulnerable to oxidation [57]. MFH employing fine magnetic particles was first investigated by Gilchrist et al. [9]. This work was followed by several in vitro and in vivo experi