## 6 Remaining Challenges, Emerging Trends, and Future Perspectives  
Nanostructured drug delivery systems in immunotherapy have shown immense potential in enhancing the effectiveness and specificity of treatments, particularly in cancer and autoimmune diseases. However, there are still significant limitations to address (Figure 9), emerging trends to consider, and future perspectives worth mentioning that are likely to shape the field. One of the challenges still faced in using nanocarriers is the achievement of high specificity in targeting immune cells. For instance, targeting precision when aiming at \begin{table}
\begin{tabular}{c c c c c c c} \hline \hline
**Compançal Name** & **Formulation** & & **Benefits** & **Indication** & **Approval** & **Company/Approval** & **Refs.** \\ \hline \multirow{6}{*}{Genexol®} & \multirow{6}{*}{Paclitaxel encapsulated in polymer micelle} & \multirow{6}{*}{Paclitaxel encapsulated in polymer micelle} & \multirow{6}{*}{Paclitaxel Potassium as an effective rod Assessmentifier when combined with radiotherapy} & \multirow{6}{*}{Metastatic breast cancer, oxoran cancer} & \multirow{6}{*}{Approved in Republic of Korea and China (2007)} & \multirow{6}{*}{Samyang Biopharm Republic of Korea)} & \multirow{6}{*}{Samyang Biopharm Republic of Korea and China (2007)} & \\  & & & & & & \\ \hline \multirow{6}{*}{Apealea®} & \multirow{6}{*}{Paclitaxel encapsulated in polymer micelle} & \multirow{6}{*}{Paclitaxel Potassium} & \multirow{6}{*}{Paclitaxel Pharmacokinetic profile} & \multirow{6}{*}{Pithelian primary peritoneal cancer, oxoran cancer, oxoran cancer, oxoran cancer, oxoran} & \multirow{6}{*}{Approved by EMA (2018)} & \multirow{6}{*}{Elevar Therapeutics (Fort Lee, NJ, USA)} & \multirow{6}{*}{Samyang Biopharm Republic of Korea)} & \\  & & & & & & \\ \hline \multirow{6}{*}{Nanoxel®} & \multirow{6}{*}{Docetaxel encapsulated in polymer micelle} & \multirow{6}{*}{Paclitaxel Potassium} & \multirow{6}{*}{Paclitaxel Potassium} & \multirow{6}{*}{Paclitaxel Potassium} & \multirow{6}{*}{Approved in India (2012)} & \multirow{6}{*}{Samyang Biopharm (Seoyoon Cheong, Republic of Korea)} & \\  & & & & & & \\ \cline{1-1} \cline{5-5}  & & & & & & \\ \hline \hline \end{tabular}
\end{table} 
Table 2: _Cont._  
Figure 9: Overview of the advantages and disadvantages of different nanostructured drug delivery systems. Created based on information from [81, 153, 173]. mucosa-resident immune cells is limited by the evolution of mucosal barriers toward blocking incoming pathogens and foreign materials [174]. Moreover, the immune system exhibits heterogeneity across patients, making it impossible to engineer one-size-fits-all nanostructured delivery systems for immunotherapeutic agents [175; 176]. Thus, fixing specificity issues and approaching treatments in a personalized manner are essential approaches in mitigating off-target effects and augmenting the efficacy of developed systems in each patient. In this respect, the advances registered in fields like genomics and proteomics can be tackled in designing personalized nanoparticles that cater to the specific immunological profile of an individual patient [177]. Another possibility for reducing off-target activity is using smart nanoparticles that can adapt to the microenvironment of the tumor or inflamed tissue. This emerging trend assumes advanced targeting mechanisms like ligand-mediated and responsive delivery, and has been increasingly exploited in recent studies [8; 28; 29; 178]. Besides this, related to the efficiency of nanoparticle-mediated immunotherapeutic systems, there is a growing trend towards developing nanoparticles that can carry multiple agents, such as drugs, genes, or imaging agents, to provide a combined therapeutic and diagnostic (theranostic) approach [81; 179]. Adverse effects can also occur when using nanoparticle-mediated immunotherapies. Some nanomaterials can be immunogenic, resulting in the unwanted and unintended activation or suppression of the immune system [18; 180].