# Recent Progress and Challenges Regarding Magnetic-Based Nanoparticles for Targeted Drug Delivery
## 4 Multifunctional Magnetite-Based Nanomaterials
The highest temperature of 72.3 \({}^{\circ}\)C was recorded for the highest concentration of the photothermal agent--magnetic NPs (5 min of irradiation, 808 nm, 2.0 W/cm\({}^{2}\)). Cytotoxicity studies confirmed the significant impact of NIR irradiation on 4T1 cell growth inhibition. It suggested that local heating facilitated BFL penetration and accumulation in cancerous cells. In turn, gelatin nanoparticles functionalized with folic acid were loaded with curcumin, magnetite NPs, and copper sulfide (CuS) [107]. CuS was responsible for an enhanced anticancer effect through NIR irradiation. Another solution involved generating local heat (MHT) in response to an alternating magnetic field (AMF) and laser (PTT) [108]. The nanoplatform for DOX delivery contained pH-sensitive poly(ethylene)glycol-poly(\(\beta\)-amino esters) and thermosensitive dipalmitoyl phosphatidylcholine. The inhibitory rate of cancer cells incubated with a DOX-loaded nanocarrier was 59.81%, which increased to 80.03% after combining MHT and PTT. Another group of multifunctional nanocarriers is designed to integrate chemotherapy and magnetic resonance imaging. A magnetic nanogel, loaded with DOX, was developed as a potential nanocarrier in HER2-positive breast cancer therapy and diagnostics [109]. The magnetic nanogel was composed of a magnetite and hydrogel hybrid structure with thermosensitive N-isopropyl acrylamide-acrylic acid, acrylic acid, and (ethylene glycol) methacrylate as hydrophilic monomers. Hereeptin antibody, targeting human epidermal growth receptor factor 2 (HER2), was also conjugated. Magnetic nanogels have the potential to be applied as probes for MRI; thus, they were used as MRI contrast agents for tumor detection. In vivo T\({}_{2}\)-weighted MR images of nude mice with breast tumors enabled the assessment of enhancement efficiency. A noticeable signal enhancement in the MCF-7 tumor region was observed after the nanogel administration, with a decrease in brightness due to magnetite NP accumulation and entering the tumor region. DOX-loaded nanogel showed a significant signal decrease as an effect of enhanced accumulation. The injection of DOX-loaded nanogel with conjugated Hereeptin resulted in a higher brightness decrease, while the increase in the T\({}_{2}\) signal confirmed further tumor targeting and accumulation. Other proposed nanocomposites for MRI, targeted DOX delivery, and cell labeling included an Fe\({}_{3}\)O\({}_{4}\) core with attached carbon quantum dots [110]. The in vitro T\({}_{2}\)-weighted MR images of water dispersed with the nanocarrier were taken for different Fe concentrations (0-0.6 mM). The MR signal intensity of T\({}_{2}\) images changed significantly with increasing iron concentration. Thus, the nanocarrier generated MR contrast due to dipolar interactions of the nanoparticle magnetic moment and protons in water. An analogous concentration-dependent darkening effect and high T\({}_{2}\)-weighted MR images at low Fe concentration were observed for the nanosystem based on a magnetite core and double-layered organic shell (poly(glycidyl methacrylate-polyethylene glycol) and salep dialdehyde) [111]. T\({}_{2}\) relaxation rates showed linearity with increasing Fe concentration (0.04-0.20 mM) and high transverse relaxivity (119 mM\({}^{-1}\)s\({}^{-1}\)). Another approach assumed magnetite core func  
Figure 7: NIR thermographic images of PTX-loaded magnetite graphene oxide functionalized by hydroxypropyl cellulose (solutions 0.25-1 mg/mL) under NIR laser irradiation (808 nm, 1.0 W/cm\({}^{2}\)). Reprinted from [105], Copyright (2023), with permission from Elsevier. tionalization with \(\beta\)-CD and further conjugation of cyclic 13 mer oligopeptide Pep42 as a targeting agent to glucose-regulated protein 78 (GRP78) overexpressed in cancer cells [112]. The presence of loaded DOX and Pep42 resulted in a decrease in breast cancer cell viability and significant induction of apoptosis.