# Recent Progress and Challenges Regarding Magnetic-Based Nanoparticles for Targeted Drug Delivery
## 4 Multifunctional Magnetite-Based Nanomaterials  
Although chemotherapy is the most often used conventional method in cancer treatment, its capability to kill tumor cells is often insufficient. Therefore, many multifunctional solutions are proposed to increase anticancer efficiency. Magnetite nanoparticles (MNPs) in the targeted delivery systems allow for chemotherapy to be combined with other methods. Some of the previously cited original papers also explored additional properties of magnetite-based nanosystems. Nevertheless, the primary emphasis was on its potential application in chemotherapy. Hence, the subsequent discussion on nanomaterials will revolve around multifunctional systems integrating chemotherapy with magnetic hyperthermia (MHT), photothermal therapy (PTT), or magnetic resonance imaging (MRI) (Table 5). In some reports, the application of hyperthermia is reduced to simple heating of samples. This procedure was used to investigate the properties of a magnetic hydrogel based on tragacanth gum [98]. The magnetite nanoparticles functionalized with amine group and folic acid were incorporated into tragacanth gum-g-polyacrylic acid copolymer crosslinked with cystamine to create a pH- and redox-responsive platform for DOX delivery. The combination of chemo and hyperthermia therapy consisted of cytotoxicity studies carried out for temperature raised to 45 \({}^{\circ}\)C in the last 2 h. The MCF 7 breast cancer cells were used for cell viability studies, and the results after 24 h showed better efficiency of pure DOX due to its burst accessibility. However, after 48 h, the DOX-loaded nanocarrier demonstrated higher anticancer performance, which was slightly improved by increasing temperature. Similarly, the same research group investigated the MCF 7 cell viability at 37 and 45 \({}^{\circ}\)C in the presence of another DOX-loaded magnetic hydrogel containing host molecule \(\beta\)-cyclodextrintrin (\(\beta\)-CD) and poly(2-ethyl-2-oxazoline) (PEtOx), ionized at the acidic cancerous environment and facilitating drug release [99]. Again, a similar anticancer activity trend was observed for free DOX, DOX-loaded hydrogel, and combining chemotherapy with hyperthermia after 24 and 48 h. On the other hand, the anticancer activity of the DOX-loaded alginate-based hydrogel was investigated in the presence of an alternating magnetic field (AMF) [100]. The potential intratumoral hydrogel included poly(lactic-_co_-glycolic acid) (PLGA) for DOX loading and Fe\({}_{3}\)O\({}_{4}\) NPs as heating agents entrapped in the alginate matrix. The nanocarrier could generate heat when subjected to AMF, and the temperature increase depends on the concentration of magnetite nanoparticles in the hydrogel. After 10 min of AMF application, the hydrogel temperature increased by 4.82 and 16 \({}^{\circ}\)C at the magnetite concentrations of 1 mg/mL and 4 mg/mL, respectively. The A549 lung cancer cells demonstrated significantly lower viability after 24 h incubation with the DOX-loaded hydrogel followed by 30 min of AFM exposure (42.92%) compared to the samples without AMF exposure (61.57%). The in vivo studies also confirmed the beneficial effect of heat generation by magnetite NPs on the tumor side. The tumor size ([width\({}^{2}\)\(\times\) length]/2) after treatment for 28 days was 1.76 and 0.46 for using only chemotherapy and combined chemotherapy with AMF, respectively, while the reference tumor (no treatment) demonstrated an average size of 3.28. Combining active drug targeting with near-infrared region (NIR, 750-1200 nm) responsiveness is another strategy for improving anticancer therapy. For this purpose, magnetite-modified graphene oxide was coated with folic acid-grafted maltodextrin [101]. The photothermal effect was studied using different concentrations of the nanocarrier and NIR (808 nm) laser with different power intensities. It was found that the temperature changed from 21.6 to 61.5 \({}^{\circ}\)C as the nanosystem concentration was 0 and 1 mg/mL, respectively.