**1. Introduction**

Although great advances in the treatment and cure of several public health issues have been developed in the last decades, cancer is still a major burden worldwide. Cancer has been the second or third leading cause of death in both the United States and Mexico over the last decade [1]. Tens of millions of people are diagnosed with cancer every year, and it is considered the main cause of death globally. In the USA, there were more than 1,700,000 new cases of cancer diagnosed in 2018, with nearly 600,000 people dying from the disease, while in Mexico it was projected that nearly 1,200,000 cancer cases will be diagnosed in the next few years. Lung cancer is the leading cause of death in the US and Mexico, and this is expected to increase in coming years. Cancer therapies include surgery, chemotherapy, and/or radiotherapy. For some types of cancer, there is also the possibility of specific targeted therapy.

Chemotherapy involves the use of nonspecific cytotoxic compounds toward cancer cells, which is why they usually have multiple serious side effects in patients [2]. In order to decrease side effects, improve bioavailability and have a selective release to tumor cells, intelligent drug delivery systems (DDS) are being developed. It is important to understand that DDS should avoid high nonspecific accumulation in tissues [3]. In addition, it is important that the material of the drug carrier should be biocompatible. Furthermore, a sufficient dose of API (active pharmaceutical ingredient) should be loaded into the system and the release of the drug should be achieved without premature leakage. That way, the API could be delivered to the target site in a controlled manner; maintaining an adequate release rate in order to achieve an effective local concentration of the drug [4].

The development of new nanomaterials for biomedical applications is a rapidly growing area of research. The use of nanoparticles (NPs) as drug carriers may present different advantages, such as protecting the drug from degradation, reducing renal clearance, as well as allowing specific bioaccumulation in cancerous tumors due to improved permeation and retention effect (EPR). Magnetic nanoparticles (MNPs), in particular, iron-based ferrites are highly attractive as their magnetic properties can be easily tuned by controlling the type and ratio of metal ion substituents. Many of them have been found to be highly stable, even at physiological conditions, as well as biocompatible. Their small size may allow them to pass through several biological barriers, increasing their systemic circulation and enhancing biodistribution. Rare-earth ions can be embedded into the crystal lattice, making possible their transmutation into beta or gamma emitters by neutron activation. Also, the large surface of the mesoporous material can be used for the immobilization of different types of fluorescent dyes or biomarkers that improve both traceability and molecular recognition specificity. Localizing with precision a tumor site, either using a radiation detector or the luminescence of the nanomaterial, could be of great value for targeted delivery, helping to minimize the amount of radiation or the chemotherapeutic agent that the patient receives, thus reducing the undesirable side effects. There are several examples of nanomaterials used to deliver radionuclides *in vivo* [5]. However, controlling size to achieve an enhanced permeability and retention effect (EPR) as well as functionalization and targeted delivery remain challenges. The incorporation of radioactive isotopes into the spinel crystal structure of magnetic ferrites is a good option to achieve that goal, without compromising the size, biocompatibility, stability, or magnetic properties of the proposed nanomaterials. Another strategy could be doping the mesoporous structure around the MNPs with the radioisotope ions. That may be achieved either by adding the radioisotopecontaining metal salts during the mesoporous phase synthesis or by dispersing and trapping the ions into the mesoporous structure once the material is formed. The high surface area or the mesoporous structure, depending on the choice of chemical composition and crystalline phase, may present the advantage to be easily functionalized with either radiosensitizers, fluorescent dyes, and/or to trap into the mesoporous structure different types of chemotherapeutic agents to further reduce the amount of radiation required to eliminate a tumor. In particular, the chances to improve bioavailability and aqueous dispersibility of low soluble chemotherapeutic agents make these magnetic mesoporous composites of great value for the transport and delivery of several promising anticancer drugs that have poor water solubilities, such as taxanes (paclitaxel, docetaxel), platinum-based drugs, curcumin, and many others (**Figure 1**). This is important, as poorly water-soluble drugs usually require the use of a high concentration of surfactants and co-solvents, or the administration of doses of the drug for longer periods, leading to adverse side effects [6].

Therefore, the development of new strategies for the treatment of this disease is urgently needed. The development of functionalized nanoparticles for both

*Designing Magnetic Mesoporous Nanoparticles for Cancer Therapy DOI: http://dx.doi.org/10.5772/intechopen.99973*

### **Figure 1.**

*Examples of cytotoxic agents used for cancer chemotherapy that present low solubility and, therefore, bioavailability problems.*

medical imaging, diagnosis, chemo- and radio-therapeutic therapies depends in part on effective tumor targeting. Conventional approaches using tumor binding ligands have been effective in cell cultures but have been disappointing *in vivo*. Nonconventional targeting, such as magnetic nanoparticles (MNPs), are promising but in the early stages of development. The preparation of magnetic nanoparticles is a very attractive and active research field. In addition to advanced clinical treatments in modern anticancer therapies, MNPs can be used in several other practical applications such as biomarkers, magnetic storage, biomolecule separation, sensors, and medical imaging contrast agents. In particular, superparamagnetic iron oxide nanoparticles (SPIONs) offer high biocompatibility than other MNPs such as maghemite and have been widely used in several biomedical applications. Although some biocompatible, nanostructured MNPs with excellent stability, improved magnetic properties, and good biodistribution have received approval for clinical use, such as Feridex®, Resovist®, Sinerem®, Clariscan®, and Lumirem®, they are currently discontinued for biomedical use as MRI agents due to potential harmful side effects following administration [7]. However, their potential use as therapeutic agents may still make these materials clinically viable agents, as less MNPs would be required, compared to MRI use, reducing potential side effects; carefully checking of toxicity and biocompatibility is a must for these magnetic materials in order to look for real clinical applications. MNPs require them to be superparamagnetic in order to avoid spontaneous aggregation *in vivo* while they move through systemic circulation through the body. Aside from the potential use MNPs as MRI contrast agents, they can be used for drug transport and delivery, as well as for magnetic heat generation (hyperthermia). The advantages of MNPs in nanoscale delivery systems are numerous—drug delivery can be enhanced, increasing the biodistribution of the nanocarrier by avoiding clearance due to their small size and stability in physiological conditions. MNPs can be chemically modified in their surfaces by attaching functional molecules, such as proteins, antibodies, peptides, or sugars, in order to enhance bioselectivity and achieve fine-tuned drug delivery and bioaccumulation in specific targets, in particular in tumor tissues [8].

The magnetic response of MNPs can be controlled by transition metal ion substitution in the crystal lattice, a strategy highly exploited for the preparation of numerous magnetic ferrites with spinel structure [9]. Substitution using transition metal and rare-earth elements is an active field of research, looking to enhance saturation magnetization (*M*s), permittivity, permeability, and blocking temperature (*T*B). Several works available in the scientific literature report the design of small MNPs with controlled magnetic properties and low dispersion, with sizes less than 35 nm, by the formation of core-shell structures using the co-precipitation method [10, 11].

As a proof of concept of this idea, iron oxide nanoparticles containing Ho(iii) were neutron activated and injected into athymic nude mice having tumors of non-small cell lung cancer (NSCLC) A549 cells [5]. A 12,000 Gauss magnet was placed on the tumor for 4 hours to allow the Ho-doped magnetic nanomaterial to collect in the tumor. There was a statistically significant reduction in the tumor size after 30 days and a 10-fold increase in Ho accumulation in the tumor with the magnet. While these results were promising, the Ho-doped magnetic nanomaterial presented several problems including the difficulty to functionalize the surface, as well as their relatively large size, which may lower the chances for cell internalization and efficient biodistribution. Furthermore, the low-intensity magnetic properties may not be appropriate to reach tumors below the surface. The ability to functionalize the surface of the MNP allows for the introduction of radiosensitizers and chemotherapeutic drugs as well as promote the suspension of the MNPs. The size is important to achieve the enhanced permeability and retention (EPR) effect for tumor penetration. Finally, the magnetic properties are important because treatment of certain cancers such as lung cancer may require the MNPs to be directed by a magnet several centimeters away.
