# Recent Progress and Challenges Regarding Magnetic-Based Nanoparticles for Targeted Drug Delivery
## 3.3. **Magnetite-Based Nanomaterials for Specific Cancer Treatment**
### Breast Cancer Treatment
The nanocarrier showed a cytotoxic effect at low concentrations (2 ug/mL), and the suggested mechanism was based on physical cell trapping within aggregating nanoparticles in a suspension. The application of other natural polysaccharides, such as alginate, was presented in synthesizing pH- and redox-responsive magnetic hydrogel for targeted DOX delivery [48]. Initially, alginate was oxidized, while magnetite was covered with silane-bearing amine functional groups. The DOX-loaded magnetic hydrogel was synthesized by employing amine-modified magnetite and cystamine, subsequently crosslinked with calcium ions. Figure 3: Schematic representation of synthetic procedure of mesoporous magnetic nanocarrier for doxorubicin delivery to breast cancer cell line. Reprinted from [46], Copyright (2023), with permission from Elsevier. The in vitro DOX release was investigated under acidic and reduction conditions. In acidic media, the hydrogel shrank, while in glutathione (GSH; overproduced in many cancerous cells) solution, disulfide bonds in cystamine were reduced, resulting in increased DOX release. The hydrogel could strongly interact with human serum albumin (HSA) due to the high affinity of hydrogel biomaterials to HAS protein. As a consequence of protein- biomaterial interactions, characteristics of biomolecules undergo significant modifications. Therefore, the fluorescence emission intensity of HSA decreased with increasing hydrogel concentration. Thus, the nanocarried acted as a quencher via a dynamic mechanism and probably caused structural changes in HSA (unfolding of protein structure on the hydrogel surface). On the other hand, a derivative of another polysaccharide, carboxymethyl chitosan, combined with a derivative of aromatic natural polymer-aminated lignocellulosic was used to fabricate pH-responsive nanoparticles with uniform size [49]. Lignin with a polyphenol structure contains many reactive functional groups; thus, it can be easily modified. It is also biocompatible and biodegradable, demonstrating antioxidant, antibacterial, and anti-inflammatory properties. On the other hand, chitosan--a cationic polysaccharide--demonstrates pH responsiveness and improves drug internalization into cells. Two modified polymers were immobilized on a magnetite core. Aminated lignocellulosic resulted in electrostatic repulsion and steric hindrance between the magnetite-based NPs, protecting them against aggregation. MTT assay and live/dead staining experiments proved that a DOX-loaded nanocarried inhibited cancer cell growth, and cell viability decreased with increasing concentrations of the drug-loaded delivery system. Besides natural polymers, synthetic polymer units have also been introduced in recently published original papers. Fe\({}_{3}\)O\({}_{4}\)@SiO\({}_{2}\) nanoparticles were subjected to coating with DOX-imprinted poly(methacrylic acid-_co_-diallyl dimethylammonium chloride) to form a cationic magnetic nanocomposite [50]. Commonly, cancer cells are characterized by a negative charge; thus, a positively charged nanocarried should penetrate such cells more efficiently. Importantly, molecularly imprinted polymer synthesized with a template molecule (DOX) guarantees high drug loading efficiency. Histopathological analysis showed the system's effectiveness in preventing tumor cell proliferation and increasing apoptosis while maintaining a limited influence on other tissues. On the other hand, poly(N-isopropyl acrylamide) (PNIPAM) was used for the fabrication of a thermosensitive magnetic nanocarrier [51]. PNIPAM undergoes transitions in response to temperature (LCST 32-34 \({}^{\circ}\)C). PNIPAM chains are water soluble below the LCST, collapse around the LCST, and above the LCTS, the interactions between chains and water molecules destroy hydrogen bonds. Therefore, the DOX release was analyzed at 30 (below), 34 (around), and 38 (above)\({}^{\circ}\)C. The highest cumulative release was observed at 30 \({}^{\circ}\)C due to physical interactions between polymer chains and water molecules.