# Recent Progress and Challenges Regarding Magnetic-Based Nanoparticles for Targeted Drug Delivery
## 3.3. **Magnetite-Based Nanomaterials for Specific Cancer Treatment**
### Treatment of Other Cancers
Simple, PEG-coated magnetite nanoparticles were used for SFB loading and characterized for potential application in liver cancer treatment [75]. The presence of PEG was beneficial for better stability, biocompatibility, lower toxic and pharmacokinetic effects. The incorporation of SFB in the nanocarir improved its anticancer activity towards HepG2 cancer cells. Analogous components in different formulations were used to fabricate PEG-modified nanoparticles to co-encapsulate magnetite nanoparticles and SFB [76]. Magnetic NPs and SFB were loaded into PEG solid lipid nanoparticles prepared using an oil-in-water homogenization process. The anticancer activity of the SFB-loaded NPs was more effective than free SFB after exceeding 48 h of cell incubation. Importantly, under-skin micromagnets were implanted (in vivo) above the liver to ensure SFB accumulation in liver cancer cells. The impact of magnetic field topographies was evaluated using two different magnet configurations--joined magnets and two magnets separated by a Teflon spacer. Two-dimensional simulation analysis and in vivo studies with sleeping mice placed on the XYZ-3-axis micropositioner stage showed higher attractive forces acting on the magnetic nanoparticles when two magnets were separated (higher magnetic field gradient). Consequently, this topography ensured the highest targeting efficacy and showed the importance of this parameter on the magnetic targeting performance. In other reports, zinc-aluminum layered double hydroxide (Zn-Al LDH) and polyvinyl alcohol were used to coat Fe\({}_{3}\)O\({}_{4}\) and, subsequently, to deliver 5-FU to HepG2 cancer cells [77]. The designed formulation was non-toxic and biocompatible with normal cells, while it showed more effective anticancer activity (dose-dependent) than free DOX. In turn, another active substance appears in studies based on PEGylated magnetite nanoparticles--crocetin (CRT) [78]. Crocus sativus L. (saffron) contains several biologically active components, including CRT, a dicarboxylic acid precursor of crocin (mono- and di-glycosl polyene ester). Crocetin was chemically bonded to PEGylated Fe\({}_{3}\)O\({}_{4}\) and demonstrated potential for reducing HepG2 cell proliferation. It was suggested that the CRT-loaded nanocarir should primarily be located in cancer tissue by passive targeting. Subsequently, degradation of PEG coating and magnetite NPs followed by free iron ions binding to ferritin proteins would result in the release of CRT. On the other hand, Au and PEGylated Fe\({}_{3}\)O\({}_{4}\) nanoparticles were tagged with two monoclonal antibodies (mAbs) for hepatocellular carcinoma-targeted therapy [79]. Avastin (AVS), mAbs against vascular endothelial growth factor, was linked to the PEGylated magnetite, while gold was tagged with mAb against cancer stem cell marker (CD90). The histopathological studies proved the best improvement in liver architecture and regression of tumors after using the system with two monoclonal antibodies compared to the one that included only AVS or nonconjugated Fe\({}_{3}\)O\({}_{4}\)-Au nanoparticles. Much like liver cancer, the mortality rate for colorectal (colon) cancer, among cancer-related deaths, is similarly high. The first-line chemotherapeutic drug for colorectal cancer treatment is 5-fluorouracil. Among 5-FU carriers, some contain the most abundant biopolymer--cellulose. It is characterized by good swelling properties, biocompatibility, and the ability of surface functionalization with different reactive groups, enabling effective drug loading. Recently, rice straw waste was used for cellulose isolation. Subsequently, magnetic cellulose bionanocomposites were fabricated for 5-FU loading and potential colorectal cancer treatment [80]. The 5-FU-loaded nanocarir demonstrated better selectivity towards two colorectal cancer cell lines (HCT116, HT29) compared to colon normal cell lines than the pure drug. In vitro studies in tumor spheroidal models suggested effective penetration of the magnetic carrier into the tumors.