# Recent Progress and Challenges Regarding Magnetic-Based Nanoparticles for Targeted Drug Delivery
## 6 Perspectives for Future Studies  
Over the years, the preparation of systems based on magnetite nanoparticles for the targeted delivery of active compounds has developed significantly in research laboratories. Through ongoing advancements in this research field, expertise has been acquired in synthesizing magnetite nanoparticles, focusing on methods and their adaptation to achieve nanoparticles of the desired shape and size. Different approaches have been developed to enhance the bioavailability of such nanosystems and protect them against aggregation. After extensive research experience, surface functionalization methods utilizing diverse ligands have been thoroughly refined. These advancements enhance targeted and controlled delivery, minimizing the systemic toxicity of active substances. It, in turn, allows for a reduction in drug doses while preserving the therapeutic efficacy. In isolated conditions, advanced DDSs show excellent responsiveness to several stimuli, such as pH, redox, or external magnetic field. Notably, the obtained nanocarriers are thoroughly characterized using numerous physicochemical methods (e.g., FTIR, XRD, SEM, TEM, VSM).  
On the other hand, the nanocarrier's functionality is primarily assessed at the laboratory level under in vitro conditions, focusing on the impact of a single factor (e.g., in vitro release studies in different pH conditions or in vitro cytotoxicity studies against selected cancer cell lines). Therefore, the general knowledge about their interaction and transformation in multicomponent biological environments is limited. The impact of protein corona on diminishing targeted delivery to the tumor microenvironment is poorly comprehended. Additionally, the activity of the reticuloendothelial system, responsible for eliminating foreign materials from biological systems, could substantially contribute to diminishing the effectiveness of the nanocarrier. Therefore, based on the results obtained  
Figure 9: Changes in the structure and intensity of ESR spectra in the endocytosis process of the functionalized nanoparticles in a cell: (**A**)—ESR signal from the spin label not bonded to cells; (**B**)—the spin label attached to a cell; (**C**)—the spin label located inside cells (in organelles such as endosome or lysosome); (**D**)—the spin label probably present in cellular mitochondria. Adapted from [134], _International Journal of Molecular Sciences_ (2020).  
on single-component isolated models, it is difficult to predict the behavior of materials after introduction into a living organism. The economic aspect is undoubtedly a significant barrier. However, from the scientific side, an important issue that could contribute to progress in this area is the development of analytical methods enabling the tracking and interpreting of interactions in multicomponent biological systems. The second aspect that demands further exploration to enhance the efficacy of clinical trials involves comprehending and adeptly monitoring the desorption process of active substances from nanocarriers within a targeted environment after cellular uptake. Finally, controlling magnetite-based nanoparticles using an external magnetic field as a medium to direct them to the targeted area also requires the development of suitable methods so that their effectiveness is not limited only to subcutaneous tissues. However, in the authors' opinion, despite the many challenges still facing the scientific community, further development of targeted DDSs based on magnetite NPs has excellent potential for practical implementation. The general achievements and challenges in research on magnetite-based NPs for targeted drug delivery are summarized in Figure 10.