# Magnetic Nanomaterials for Magnetically-Aided Drug Delivery and Hyperthermia
## 1 Introduction  
Using magnetic nanomaterials for drug delivery strategies has become a promising and effective method in animal models for cancer and other diseases [1; 2], although no clinical method has obtained FDA approval to date [3]. The endeavor to utilize magnetic nanoparticles for the purpose of drug delivery in humans for curing various types of diseases started in 1996 [4]. Since then, numerous research groups have been involved in developing multiple types of approaches and tailored synthetic techniques for diverse types of magnetic nanomaterials to meet the drug delivery requirements. Some designs and techniques were successful, others were not [3]. In this review, we will discuss the most important designs of magnetic nanomaterials with regard to gene and drug delivery. Magnetic nanoparticles have specific characteristics, such as small particle size, large specific surface area, and superparamagnetism [5]. Iron oxide nanoparticles are among the most frequently used nanomaterials [5]. They include magnetite (Fe\({}_{3}\)O\({}_{4}\)) and maghemite (\(\gamma\)-Fe\({}_{2}\)O\({}_{3}\)) nanoparticles [6]. Magnetic nanoparticles play a big role in cancer detection [7; 8; 9], drug delivery [2; 3], as well as hyperthermia treatment [10; 11; 12]. During the last decade, bi-magnetic core/shell nanoparticles featuring an iron core and an iron oxide (Fe\({}_{3}\)O\({}_{4}\)) shell have become widely used [13; 14; 15; 16; 17; 18; 19], due to their superior magnetic properties [20; 21]. As discussed above, magnetic nanoparticles have small diameters (\(<\)100 nm) so they can effectively extravasate [22] and target diseased areas [6], such as infected tissue (lesions) or tumor tissue. The mechanism of extravasation has been established in mouse models [22]. However, enhanced permeation and retention (EPR) is significantly less efficient in humans than in rodents [22; 23; 24]. Furthermore, there is significant variability of EPR among individual patients and various tumor types. The strength of EPR is also dependent on the lengths of treatment with nanoformulations against cancer [23; 24]. Therefore, magnetic forces can be, principally, used to aid targeted drug delivery [3]. Due to their nanoscopic size, magnetic nanoparticles have very high surface areas (\(>\)100 m\({}^{2}\)/g) and are, therefore, suitable to transport significant adsorbed or tethered payloads (\(>\)10% by weight). The general disadvantage of the high surface areas of magnetic nanoparticles is corona formation [25; 26], which is prevalent in living systems. Magnetic nanoparticles play a major role in tumor imaging [6]. Magnetic resonance imaging (MRI) [27] uses superparamagnetic iron oxide nanoparticles as contrast agents [6]. Compared togadolinium(III)-based contrast agents, iron oxide-based imaging tools have lower nephro- and cytotoxicities, which is advantageous [28]. Until recently, iron oxide-based imaging agents were limited to T2-based imaging (spin-spin relaxation [29]), whereas gadolinium(III)-based imaging modalities are capable of T1-based imaging (spin-gitter relaxation [29]), which is generally perceived as advantageous, because it provides positive imaging contrast. However, this has changed since the arrival of ultrasmall Fe\({}_{2}\)O\({}_{3}\) clusters, which permit T1-based imaging [30; 31]. Magnetic nanoparticles as drug carriers are also becoming very important for medical applications when the drug molecules have to target a specific location _in vivo_. In most published applications, magnetic nanoparticles are used as drug carriers in conjunction with tethered antibodies and chemotherapeutic drugs [6]. For example, antibody-conjugated fluorescent magnetic nanoparticles were used for targeted imaging and simultaneous therapy of gastric cancer [32], and reducible polyamidoamine-magnetic iron oxide self-assembled nanoparticles were used for doxorubicin delivery for cancer therapy [33].