Biomedical Engineering Reference
In-Depth Information
17
Magnetic Nanoparticles
for Cancer Therapy
17.1 Introduction ............................................................................................................................ 293
17.2 Scientific Background ............................................................................................................ 294
Physical Principles • Effects of AC Magnetic Fields in Human Application: Calculations
and Clinical Experience • Activation of Iron Oxide Nanoparticles in Alternating Magnetic
Fields • Alternating Magnetic Field Generation
17.3 Synthesis and Modification of Iron Oxide Nanoparticles ................................................301
Synthesis and Core-Shell Structures • Characterization
17.4 Biological Effects ..................................................................................................................... 303
Effects of Nanoparticle Surface Coating • Thermal Dose In Vitro • Thermal Dose In Vivo
17.5 Clinical Application in Cancer Therapy ............................................................................. 307
Components of a Clinical MFH Thermotherapy System • Clinical Results
17.6 What Comes Next? ..................................................................................................................313
References ............................................................................................................................................. 314
Michael L. Etheridge
University of Minnesota
John C. Bischof
University of Minnesota
Andreas Jordan
Charité-University Medicine
17.1 Introduction
on the correct orientation of the seeds within the applied field.
However, this early work provided important observations and
equations for understanding magnetic field and tissue interac-
tions, which have been crucial in the development of the next
phase of magnetic field-based therapies—magnetic fluid hyper-
thermia (MFH). Magnetic fluids are aqueous dispersions of
nano- or microscale particles that are excited by alternating
magnetic fields to produce localized heat and do not demon-
strate the same critical alignment problems as thermoseeds. In
addition, MFH offers significant advantages over traditional
electromagnetic-based therapies, including:
Electromagnetic field-based thermal therapies have demon-
strated the capability to selectively deposit large amounts of
energy in tissue, resulting in localized temperature increases
capable of hyperthermia and thermoablation. However, cur-
rent clinical approaches have met with considerable limitations.
Microwaves, radiofrequency (RF) waves, and lasers exhibit sig-
nificant absorption at interfaces with differing electrical properties
(Wust et al. 1991a). This results in attenuation at surfaces, issues
with focusing energy, and unintended hot spots, leading to dif-
ficulty in treating deep-seated tumors. In addition, the geometry
of the treated region is limited by the shape of the probe or array
(VanSonnenberg, McMullen, and Solbiati 2005), requiring over-
treatment of the surrounding areas or skill- and time-intensive
repositioning to ensure complete treatment of complex tumors.
It has been well characterized that low-frequency, alternating
magnetic fields show very little attenuation in biological tissues,
and it was determined that implanted, energy-absorbing materi-
als provide a means of targeting heat into deep-seated tissues.
Early studies on magnetic field-based therapies by Oleson et
al. (Oleson, Cetas, and Corry 1983; Oleson, Heusinkveld, and
Manning 1983), Brezovich et al. (Brezovich, Atkinson, and Lilly
1984; Brezovich 1988), and Stauffer et al. (Stauffer et al. 1984;
Stauffer, Cetas, and Jones 2007) utilized implanted ferromag-
netic thermal seeds (on the order of millimeters), but the appli-
cation was limited by the need to surgically implant each seed,
and because efficacy of heat generation was critically dependent
1. The potential for completely noninvasive treatment.
Nanoparticles injected intravenously could preferen-
tially collect in the tumor tissue through the enhanced
permeability and retention (EPR) effect (Iyer et al. 2006)
and tumor-specific targeting (Byrne, Betancourt, and
Brannon-Peppas 2008). These deep-seated deposits can
then be excited by an external field, with no need for sur-
gical intervention. Current MFH techniques require min-
imally invasive, interstitial injection to attain adequate
concentrations for treatment, but truly noninvasive pro-
cedures are the long-term ambition.
2. The potential capability to treat complex tumor geom-
etries, while minimizing effects to surrounding tissue.
If the tumor is preferentially loaded with nanoparticles
(either through interstitial delivery or targeting), heating
can be better confined to the region of interest.
293
