346
M. Avolio et al.
of coated spinel ferrite iron oxide MNPs of ca. 15 nm diameter, as heat mediators.
Despite the apparatus and the magnetic fluid employed demonstrated the feasibility
in clinical routine, significant benefits of MFH were obtained only in combination
with radiotherapy (RT). Indeed, studies conducted by Wust et al. [134] using the
first prototype of MagForce with different field applied on 22 patients with various
types of recurrent tumors (sarcoma, rectal cancer, cancer cervix, ovarian cancer, and
prostate cancer) previously heavily treated, led to unsatisfactory results. The SAR
achieved in the target was 60–380 W/kg, depending on the pathology and on the
maximum field applicable, but despite most of the tumor was heated to more than
40 C, the >42 °C overheating coverage was limited.
The feasibility and efficacy of the combination of MFH with standard RT on
recurrent glioblastoma multiforme was established by the studies by Maier-Hauff
et al. [132] conducted on 14 patients recruited in a phase I trial. After injection of a
suspension of 12 nm iron oxide MNPs coated by aminosilane in the tumor, recursive
sessions of MFH (median 6) and RT (median 30 Gy, by 2 Gy per session) were
carried out. The combination treatment was well tolerated by all patients with minor
or none side effects. The median maximum intratumoral temperature was 44.6 °C
and the 90% of the tumor experienced a temperature over 40.5 °C, which, based
on previous results, is too low to produce significant and durable damages to the
tumor mass. In the phase II study [127] conducted on 59 patients, the MFH (twice
weekly) and RT (five times/week) treatments were repeated with the same modality
after direct injection of the MNPs suspension into recurrent glioblastomas. The main
result concerning the patient survival is promising as the median overall survival
(13.4 months) is more than the double of the typical 6 months median survival
recorded in these cases [135, 136].
14.6 Conclusions
The increased ability in manipulating matter at the nanoscale has paved the way
towards the creation of a plethora of novel systems endowed with extremely appealing
properties exploitable in a wide number of clinical applications, the two most prominent being magnetic resonance imaging and magnetic fluid hyperthermia. In this
chapter, we reviewed a few recent examples to convey to the reader a picture of the
promising role MNPs may play in the medicine of the next future. Nevertheless,
the exploitation of the full clinical potential of MNPs still requires addressing some
major issues, mostly related to the complex interaction with the human body. Despite
the countless examples of promising MNP-based materials, indeed, the translation
to clinics is still limited to few, although effective, examples.
A major challenge is represented by site-specific delivery of a large enough amount
of material via a systemic route, such as intravenous injection, which is opposed by
the many biological barriers seizing foreign objects in the liver and spleen. On the
other hand, a better understanding of the multifaceted MNP-cell interplay, is also
mandatory to reach the goal. The solution of such a complex problem requires the
M. Avolio et al.
of coated spinel ferrite iron oxide MNPs of ca. 15 nm diameter, as heat mediators.
Despite the apparatus and the magnetic fluid employed demonstrated the feasibility
in clinical routine, significant benefits of MFH were obtained only in combination
with radiotherapy (RT). Indeed, studies conducted by Wust et al. [134] using the
first prototype of MagForce with different field applied on 22 patients with various
types of recurrent tumors (sarcoma, rectal cancer, cancer cervix, ovarian cancer, and
prostate cancer) previously heavily treated, led to unsatisfactory results. The SAR
achieved in the target was 60–380 W/kg, depending on the pathology and on the
maximum field applicable, but despite most of the tumor was heated to more than
40 C, the >42 °C overheating coverage was limited.
The feasibility and efficacy of the combination of MFH with standard RT on
recurrent glioblastoma multiforme was established by the studies by Maier-Hauff
et al. [132] conducted on 14 patients recruited in a phase I trial. After injection of a
suspension of 12 nm iron oxide MNPs coated by aminosilane in the tumor, recursive
sessions of MFH (median 6) and RT (median 30 Gy, by 2 Gy per session) were
carried out. The combination treatment was well tolerated by all patients with minor
or none side effects. The median maximum intratumoral temperature was 44.6 °C
and the 90% of the tumor experienced a temperature over 40.5 °C, which, based
on previous results, is too low to produce significant and durable damages to the
tumor mass. In the phase II study [127] conducted on 59 patients, the MFH (twice
weekly) and RT (five times/week) treatments were repeated with the same modality
after direct injection of the MNPs suspension into recurrent glioblastomas. The main
result concerning the patient survival is promising as the median overall survival
(13.4 months) is more than the double of the typical 6 months median survival
recorded in these cases [135, 136].
14.6 Conclusions
The increased ability in manipulating matter at the nanoscale has paved the way
towards the creation of a plethora of novel systems endowed with extremely appealing
properties exploitable in a wide number of clinical applications, the two most prominent being magnetic resonance imaging and magnetic fluid hyperthermia. In this
chapter, we reviewed a few recent examples to convey to the reader a picture of the
promising role MNPs may play in the medicine of the next future. Nevertheless,
the exploitation of the full clinical potential of MNPs still requires addressing some
major issues, mostly related to the complex interaction with the human body. Despite
the countless examples of promising MNP-based materials, indeed, the translation
to clinics is still limited to few, although effective, examples.
A major challenge is represented by site-specific delivery of a large enough amount
of material via a systemic route, such as intravenous injection, which is opposed by
the many biological barriers seizing foreign objects in the liver and spleen. On the
other hand, a better understanding of the multifaceted MNP-cell interplay, is also
mandatory to reach the goal. The solution of such a complex problem requires the