## 6 Remaining Challenges, Emerging Trends, and Future Perspectives
The ways in which innate and adaptive immune systems interact with nanomaterials are not yet fully understood, necessitating in-depth research for better comprehending and controlling the immunogenicity of nanoparticles [181; 182; 183]. Until then, ensuring that nanomaterials do not elicit harmful immune responses remains a challenge. Emerging trends for solving the biocompatibility issue revolve around creating biomimetic nanoparticles. Specifically, cell-mimicking nanoparticles may be used as carriers for immunotherapeutic agents, evading the immune system or enhancing immune targeting due to their similar features with immune cells or pathogens [178; 184; 185]. Another possibility is to employ natural carriers, such as exosomes and cell membrane-based nanoparticles, which benefit from inherent biocompatibility and targeting potential [178; 186]. Other remaining challenges to be solved before translating nanoparticle-based delivery systems to clinical practice include the stability and shelf-life of the formulations, regulatory and safety concerns, and the scalability of the fabrication methods. In more detail, factors like storage conditions, long-term effects, safety, and efficacy standards must be clearly established before producing complex multifunctional nanoparticulated systems at an industrial scale. Additionally, at a large scale, manufacturing processes may lead to high costs, limiting their widespread adoption [187; 188; 189; 185]. As concerns future perspectives, they should be envisaged in correlation with the existing framework and the \"open threads\" left from current nanoformulations proposed for immunotherapy. One possibility is to optimize the nanosystems developed years ago and \"abandoned\" at in vitro/in vivo testing stages despite obtaining encouraging results at the time. More in-depth research is required to address the identified challenges and move further with the progression of innovative nanomedicines toward clinical studies, eventually bringing new market options. In connection with these aspects, artificial intelligence and machine learning can be used in predicting and optimizing the interactions between nanoparticles and the immune system. These technologies can actively contribute to engineering more effective and personalized nanostructured delivery systems, aiding in drug design through their ability to adapt surplus amounts of data available for generating meaningful insights [190]. Another appealing possibility for bringing about progress in nanoparticle-mediated immunotherapy is its integration with advanced therapies like CRISPR and gene editing. Gene editing represents a cutting-edge technology in the field of gene therapy technologies. CRISPR technology has revolutionized cancer treatment by offering new therapeutic alternatives, particularly in the field of cancer immunotherapy. Therefore, scientists are strongly driven to develop a remedy for numerous challenging disorders through the utilization of CRISPR technology. Nonetheless, several obstacles persist and require resolutions for the effective implementation of gene editing [66; 191; 192]. Interesting developments in the field may also be foreseen once the fabrication of uniform nanoparticles with controllable features is achieved though low-cost, energy-efficient methods. This is an essential aspect that needs to be solved to ensure nanostructured drug delivery systems' scalability while also considering the production processes' environmental impact. One potential solution is to use microfluidic synthesis to diminish reagent consumption, reduce waste generation, and limit batch-to-batch variations [193]. Future perspectives should also reflect upon the public perception and adoption of newly developed immunotherapeutic alternatives. Increasing the public's awareness and understanding of nanomedicine's benefits and risks is essential for building trust and support for these emerging technologies.