# 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
Caspase assay indicated that the drug-loaded carrier could induce apoptosis in both colorectal cancer cells, while mitochondrial membrane potential assay showed a slight impact on mitochondrial function. The toxicity to red blood cells was insignificant. However, the anticancer activity in a model mimicking tumor- vasculature-drug interaction upon drug delivery was reduced (the percent inhibition below 50%) due to the tumor microenvironment, suggesting the need to improve the nanocarir. Another 5-FU targeted delivery system comprised a magnetic triblock (PEG- poly-\(\epsilon\)-caprolactone, PCL-PEG) copolymer with conjugated folic acid as a targeting ligand [81]. PCL hydrolyzes to 6-hydroxycapric acid, a natural metabolite in the body, but the process is very slow. PCL copolymerization with PEG should ensure crystallinity, permeability, and polymer solubility, resulting in faster degradation. The drug release was prolonged, which suggested a 5-FU location in the core region. The inhibitory effect of the 5-FU-loaded nanocarrier was investigated against different colon cancer cell lines (HCT116, SW480, HT29, Caco-2). The half-maximum inhibitory concentration values of the drug-loaded material for colon cancer cells were significantly lower than that of free 5-FU. Therefore, reduced drug doses could be used to inhibit cancer cells. The quantitative in vitro cellular uptake was evaluated by measuring Fe concentration, while in vivo studies were carried out by comparison of colon tumor tissues. The average iron content in HT29 cell lines, considered the most 5-FU-resistant colon cancer cell line, was about four times higher than in normal cells, reflected by the carrier accumulation in tumor tissue. Polate-mediated endocytosis was indicated as dominant in HT29 cells. This ligand-receptor interaction is considered a more efficient endocytosis type for drug distribution in colon tumors. Additionally, a significant inhibition of tumor volume was observed after 30 days, and the survival time of tumor-bearing mice was higher (48 days) than for mice treated with pristine 5-FU. Further research on this system was intended for targeted magnetochemotherapy [82]. There are also limited reports employing alternative active substances against colon cancer cells. Chitosan-coated magnetite nanoparticles were applied for targeted delivery of oxaliplatin (OXA) and irinotecan (IRI) [83]. However, the magnetite nanoparticle synthesis protocol assumed a coprecipitation method with chia seed nucilage as a capping agent in water. The preliminary studies using CT26 colorectal cancer cells showed promising anticancer activity of the OXA-IRI-loaded nanocarrier. Another polysaccharide, pectin (PET), was adopted for the preparation of oral magnetically driven PET nanoparticles for chlorogenic acid (CGA) targeted delivery to colon cancer (Figure 6) [84]. The magnetite covered with oleic acid (Fe3O4@OA) was responsible for magnetic response, while citrus pectin was responsible for CGA encapsulation. Pectin can effectively bind drugs through different bonds (covalent, ionic, hydrogen) and prevents drug release due to gelation and crosslinking. However, it is sensitive to pectinase produced in the colon. The proposed mechanism assumes that the orally administrated nanocarrier is targeted to the colon by external magnetic field. During PET/CGA/Fe3O4@OA movement, the outer layer of pectin protects CGA from an acidic environment of upper gastrointestinal track (stomach, small intestine), and finally the nanocarrier degrades in the colon due to pectinase, resulting in the drug release. Cervical cancer is the fourth most common malignant gynecological tumor in women, and nearly 50% of cases affect women under 58 [85]. There have recently been few  
Figure 6: The synthetic procedure and proposed mechanism of chlorogenic acid’s oral magnetically driven delivery system. Adapted from [84], Copyright (2023), with permission from Elsevier. reports of new magnetic carriers for targeted therapy in this area.