**2. Size, morphology, and magnetic properties of nanoferrites for drug delivery in cancer**

The size, morphology, and magnetic properties of nanoparticles in drug delivery applications, have been identified as keys parameters in the literature [1, 2]. The easy way to tune these properties is from the synthetic routes [15]. The growth mechanism involved in the final morphology and structure is not completely clear. The conditions synthesis and their correlation with the physicochemical properties have been discussed in the literature [16]. Here, we focus on the recent advances in morphology, size, magnetic properties, and their relationship with the synthetic routes of nanoferrites used in drug delivery for cancer. **Table A1** shows a summary of these properties recently reported in the literature. For there, it is clear that the synthetic routes more employed for nanoferrites synthesis are:


#### **Figure 1.**

*Transmission Electron microscopy (TEM) images for a) calcium ferrite nanoparticles with a size of 5 nm, reproduced from Ref. [17] with permission of the editors, b) magnetite hollow spheres of diameter 350 nm, reproduced from Ref. [65] with permission of the editors, c) magnetite nanorods, reproduced from Ref. [48] with permission of the editors, and d) magnetite hexagonal nanoparticles, reproduced from Ref. [56] with permission of the editors. Copyright 2019 MDPI, 2016 Nature, 2020 Elsevier, and 2021 the Royal Society of Chemistry.*


Tripathy et al. [14] reported a comparison among the different techniques for ferrite nanoparticles obtention.

Based on some scientific reports, nanoferrites used in cancer drug delivery applications range from 5.2 *nm* to 300 *nm* (**Table A1**). Calcium ferrite (CaFe2O4) obtained by coprecipitation is the smallest nanostructure system. Magnetite (Fe3O4) fabricate from the solvothermal method is the larger one (**Figure 1**). However, particles larger than 200 *nm* segregate by mechanical filtering and eventually get removed by phagocytic cells. Nanoparticles with sizes smaller than 10 nm lead to renal filtration and accumulation into the fenestration of the kidneys' glomerular endothelium. Therefore, the most effective drug delivery agents possess sizes ranging between 10 and 100 nm [68]. However, Sivaraj et al. [69] suggest that the nuclear membrane pores allow entry of nanoparticles with a size below 9 *nm*. Nanoparticles penetration into the cells may be maximized by surface functionalization with small molecules (e.g. folate, proteins, peptides, antibodies, and aptamers). This penetration induces receptor-mediated endocytosis, caveolaemediated endocytosis, lipid raft mediated endocytosis, and/or micropinocytosis. After endocytosis in cancer therapy, nanomaterial releases maximum drug to inhibit the DNA/RNA synthesis and mitochondria damage.

The most common ferrite nanoparticles use for cancer drug delivery systems ranging from 20 *nm* to 30 *nm* (**Table A1**). Moreover, the most popular morphology


#### **Table 1.**

*Summary of spherical nanoparticles ferrite type (*FT*) obtained by different methods with their sizes (*S *in* nm*), saturation magnetization (*MS *in* emu/g*), coercivity (*HC *in* Oe*), and remanence (*MR *in* emu/g*), reported in the literature. All the magnetic properties were reported at room temperature.*

*Nanoferrites-Based Drug Delivery Systems as Adjuvant Therapy for Cancer Treatments.… DOI: http://dx.doi.org/10.5772/intechopen.100225*

obtained from the synthetic routes is spherical particles (**Table 1**). Nanorods and particles with hexagonal shapes are the less common nanostructures used for drug delivery in cancer applications (**Figure 1**).

A complete understanding of magnetic properties is essential for a proper implementation of nanoferrites in drug delivery applications [6]. The saturation magnetization (*Ms*), coercive force (*HC*), and remanence (*MR*) are the most popular magnetic parameters reported for nanoferrites to cancer drug delivery applications (**Table A1**). Nanoferrites with the highest magnetic response (*Ms*) are cobalt ferrite (CoFe2O4) with a size of 15 *nm* obtained by sonochemical technique [28]. The smallest saturation magnetization was reported to zinc ferrite (ZnFe2O4) nanostructures (75 *nm*), which were synthesized by the sol–gel method [53]. Usually, nanoferrites used in cancer drug delivery applications show superparamagnetic behavior. Superparamagnetic nanoparticles evidence zero coercivity and remanence at temperatures above the blocking one (**Table 1**). In other cases, ferrite nanostructures with coercivity as high as 3409 *Oe* are used in cancer drug delivery applications (CoFe2O4 nanofibers with a diameter of 50 *nm* [45]. Moreover, cobalt ferrite nanoparticles show the highest magnetic remanence of 30.2 *emu/g* with a size of 30 *nm* obtained by thermal decomposition (**Table 1**).
