# Recent Progress and Challenges Regarding Magnetic-Based Nanoparticles for Targeted Drug Delivery
## 3.3. **Magnetite-Based Nanomaterials for Specific Cancer Treatment**
### Breast Cancer Treatment
Epithelial cell adhesion molecule (EpCAM) is overexpressed in many human cancer cells; thus, it was chosen as a specific DNA aptamer. Magnetite nanoparticles were covered with gold and cysteamine. Subsequently, PTX was modified to introduce carboxyl groups and disulfide bonds (PTX-S-S-COOH) and finally reacted with amine groups of cysteamine. Additionally, thiol-modified aptamer was also conjugated to the magnetic nanocarrier. Specific aptamer molecules facilitated drug delivery into EpCAM-positive cells, enhancing cytotoxicity against MCF 7 and 4T1 cancer cells, while limiting toxicity to reference normal breast cell line MCF-10A without EpCAM. Flow cytometry studies confirmed that the nanocarrier with the aptamer did not enter MCF-10A cells; thus, internalization of Fe\({}_{3}\)O\({}_{4}\)@PTX-Apt in EpCAM positive cells was significantly higher compared to reference Fe\({}_{3}\)O\({}_{4}\)@PTX. The breast cancer MCF 7 cell lines were also used to investigate magnetite nanoparticles functionalized with L-cysteine and hyaluronic acid loaded with tamoxifen (TMX)--a drug belonging to the selective estrogen receptor modulators [64]. Hyaluronic acid is often selected due to its high affinity towards the cluster determinant 44 (CD 44) receptor, overexpressed on the surface of many cancer cells, while the presence of amino acids improves colloidal stability. The increased cytotoxicity of the TMX loaded in the nanocarrier against the breast cancer cells yielded an equivalent anticancer activity compared to free TMX, but at a concentration four times lower. Significantly, L-cysteine influenced enhanced anticancer activity. Some literature reports combine the design of new targeted carriers of active substances and the use of compounds of natural origin, mainly polyphenols (e.g., curcumin, quercetin), as potential agents with anticancer properties. An illustration is a complex system comprising a magnetic core designed to co-deliver hydrophilic doxorubicin and hydrophobic curcumin (CUR), Figure 5[65]. Initially, magnetite-\(\beta\)-cyclodextrinrin (Fe\({}_{3}\)O\({}_{4}\)-\(\beta\)-CD) nanocomposite was formed and covered with 3-aminopropyltrimethoxysilane to introduce amine functional groups. The triazine dendrimer (TD) shell was subsequently created in the presence of citric acid and melamine. The process of dendrimer growth was carried out until generation 2.5 was obtained (Fe\({}_{3}\)O\({}_{4}\)-\(\beta\)-CD-CTD G2.5). After that, carboxylic groups of Fe\({}_{3}\)O\({}_{4}\)-\(\beta\)-CD-CTD G2.5 reacted with amine groups of folic acid to create Fe\({}_{3}\)O\({}_{4}\)-\(\beta\)-CD-CTD-FA. The presence of cyclodextrin cavities and the branched dendrimer structure assured the high loading capacity of both active molecules. The nanocarrier demonstrated high antioxidant activity and biocompatibility against MDA-MB-231 breast cancer cells. The presence of folic acid (folate receptor-mediated endocytosis) and curcumin improved the DOX cellular uptake by breast cancer cells, increasing topoisomerase II-mediated DNA cleavage in the cytoplasm. Curcumin was also successfully encapsulated in magnetic nanoparticles to co-deliver two active agents with different polarities--CUR and piperne (PIP) [66]. PIP molecules were attached to the chitosan surface, while CUR molecules were entrapped into the zein matrix. The polymeric carrier with magnetite core was coated with chitosan to create a CUR-PIP-loaded polymer magnetic system demonstrating significant synergistic cytotoxicity against MCF 7 cells. The nanoprecipitation approach increased the bioavailability of CUR and PIP, resulting in increased toxicity to cancerous cells compared to free forms of active agents. On the other hand, a magnetite-graphene quantum dots hybrid with conjugated folic acid was investigated as a curcumin delivery system to enhance the potential drug efficiency in cancer treatment [67]. The hybridization of magnetite NPs with graphene quantum dots (GQDs) should improve the properties of the composite material.