# Recent Progress and Challenges Regarding Magnetic-Based Nanoparticles for Targeted Drug Delivery
## 2 New Hybrid Systems for Potential Targeted Delivery
Another approach involved coating the magnetic core with carbon to reduce the non-biocompatibility and toxicity of Fe\({}_{3}\)O\({}_{4}\). Subsequently, the material was functionalized with nitric acid and the surfactant Pluronic(r) F-127 to enhance colloidal stability and improve loading affinity for cationic doxorubicin [33]. A higher level of DOX loading was also achieved by MNP stabilization using \(N\)-(phosphomethyl)iminodiacetic acid (PMIDA) before silanization [34]. The proposed mechanism assumed simultaneous coordination of DOX on the PMIDA molecule and silanol groups, resulting in a synergistic effect in the drug binding. PMIDA also limited antibiotic desorption, which could be used in drug delivery systems with prolonged action. The literature also documents the development of magnetic microrobots designed to concurrently deliver multiple drugs, aiming to induce a synergistic effect in cancer therapy. The concept, underpinning the encapsulation of DOX and acetylsalicylic acid (ASA) within a magnetite microrobot, involved utilizing a composition comprising poly(ethylene glycol) diacrylate (PEGDA) and biodegradable gelatin methacryloyl (GelMA) [35]. GelMA, in combination with PEGDA, was also used to prepare magnetic microrobots with sequential dual-drug release [36]. Gemcitabine (GEM) was conjugated on the surface by a sulfide bond and initially released using near-infrared or a reducing agent (e.g., glutathione, GSH). At the same time, doxorubicin was encapsulated inside and released later during the microrobot decomposition, while magnetite nanoparticles conjugated on the surface through hydrogen bonding were easily separated using weak external stimuli. Literature reports featuring other active substances are less common because DOX predominates as a model anticancer drug. Nevertheless, these reports offer equally valuable solutions for targeted drug delivery. Epirubicin (EPI) is another anthracycline antibiotic, doxorubicin epimer, commonly applied in chemotherapy [37]. It was used as a model agent to evaluate the properties of the nanosystem composed of a magnetite core stabilized with citrate, covered with a silica shell, and decorated with silver nanoparticles [19], demonstrating antibacterial and anticancer efficacy. In the exploration of carriers for other crucial categories of anticancer drugs, there are designs of systems dedicated to antimetabolites, which include methotrexate (MTX) or 5-fluorouracil (5-FU). Functionalized graphene oxide/Fe\({}_{3}\)O\({}_{4}\) nanocomposite was proposed as a nanocarrier of MTX [38]. The superparamagnetic graphene oxide demonstrated high water solubility, and MTX delivery was improved by using cyanuric chloride as a crosslinking unit. An alternative suggestion was outlined for delivering 5-FU, involving grafting dimethylaminoethyl methacrylate onto \(\kappa\)-carrageenan. Subsequently, this copolymer was coated onto magnetite using a microwave-supported coprecipitation method [39]. On the other hand, the molecularly imprinted polymer was a strategy for targeted delivery of docetaxel (DTX)--one of the microtubule-damaging agents [40]. The diverse synthetic solutions proposed recently for targeted anticancer drug delivery using magnetite-based nanosystems, along with information on the method of magnetite synthesis and techniques for characterizing the final product, are collected in Table 2.  
Figure 2: The synthesis procedure of pH- and thermo-responsive magnetic nanoparticles loaded with doxorubicin. Reprinted from [29], _Polymers_ (2021).