# Recent Progress and Challenges Regarding Magnetic-Based Nanoparticles for Targeted Drug Delivery
## 2 New Hybrid Systems for Potential Targeted Delivery  
Effective drug delivery systems must fulfill specific criteria, encompassing high loading capacity, dispersion stability, and biocompatibility. In order to obtain a material characterized by such properties, [PERSON] et al. [26] proposed a simple solvothermal synthesis of  
Figure 1: Schematic representation of the number of original research articles (2003–2023) on magnetite-based nanoparticles based on the Scopus database (5 December 2023) using selected terms from the article title, abstract, or keywords. monodispersed Fe\({}_{3}\)O\({}_{4}\) nanospheres with a mesoporous structure and superparamagnetic features. The synthetic route proceeded in the presence of iron chloride, polyvinylpyrrolidone, and urea. The Fe\({}_{3}\)O\({}_{4}\) particles with spherical shapes demonstrated almost monodisperse sizes with an average diameter of about 207.3 nm. The material was characterized by the high loading capacity of a model drug--doxorubicin (DOX), 0.36 g/g--attributed to the strong physical adsorption and hydrogen bonding interactions. The in vitro cytotoxicity tests demonstrated the neglected effect of the delivery system on cell viability, while only the DOX-loaded nanosphere displayed a cytotoxic effect on selected cancer cells. In continuing these studies, hollow mesoporous Fe\({}_{3}\)O\({}_{4}\) nanospheres were acquired without incorporating a template [27]. The hollow structure, mesoporous shell, and rough surface facilitated high DOX loading capacity without using high initial drug concentration. However, drug delivery systems are usually much more complex, and magnetite is only one of the elements. Polymeric systems, whether natural or synthetic, possess significant potential by enabling a responsive reaction to specific stimuli. This capability facilitates the concentration of nanocarriers at a targeted site. [PERSON] et al. [28] described a synthesis procedure of magnetic nanocomposites composed of methoxy poly(ethylene glycol), MePEG, grafted to chitosan, to which backbone magnetite nanoparticles and DOX were conjugated. The nanocomposites with spherical shapes demonstrated an average size between 100 and 300 nm. As doxorubicin was attached to the delivery system through disulfide linkage, the drug release was investigated in the presence of glutathione (GSH), responsible for disulfide bond disintegration and occurring at higher levels in cancer cells than in the extracellular environment or normal cells. Therefore, the material demonstrated redox responsiveness and magnetic sensitivity. On the other hand, pH- and thermo-responsive complex nanoparticles were obtained by applying the reverse addition-fragmentation chain transfer (RAFT) polymerization method [29]. Fe\({}_{3}\)O\({}_{4}\) nanoparticles were covered with a silica layer and functionalized with amine groups using 3-aminopropyltrimethoxysilane (APS). Then, 4-cyano-4-(phenylcarbonothioylthio)pentanoic acid (CPDB) was attached as a RAFT agent. Subsequently, methacrylic acid (MAA) and \(N\)-Isopropylacrylamide (NIPAM) monomers polymerized onto the particle surface, and as-prepared PNIPAM-PMAA@Fe\({}_{3}\)O\({}_{4}\) was used for DOX loading (Figure 2). An alternative approach was employed to produce a magnetic hydrogel as a carrier for DOX. Poly(acrylic acid/acrylamide) magnetite hydrogel was prepared using radiation synthesis [30]. The hybrid structures with magnetite core could be subjected to various treatments, increasing their potential for targeted delivery of active substances. A compelling concept involves enhancing the drug loading capacity and introducing specific optical properties by decorating magnetite--previously coated with PEG for improved stability--with graphene quantum dots [31]. An alternative suggestion involves incorporating carbon dots (CDs) derived from folic acid. This solution was proposed for a complex DOX support in which Fe\({}_{3}\)O\({}_{4}\) was covered with a triazine dendrimer grafted with highly fluorescent CDs [32].