Research progress of natural cell-derived nanoparticles in immunotherapy

<sec><p indent="0mm">In recent years, natural cell-derived nanoparticles (CDNPs) have become an important tool in the biomedical field. CDNPs are widely derived from animal cells, plant cells, and microorganisms, and usually have good biocompatibility, low toxicity, and rich biological activity. CDNPs can be used as carriers to deliver immunomodulatory molecules, and can also be used to regulate local immune response depending on its immunomodulatory effect. So far, CDNPs have shown promising applications in treating various diseases such as cancer, inflammation, autoimmune diseases, etc. This review summarizes the latest research progress of CDNPs in immunotherapy, including the current application status of extracellular vesicles, platelet-derived nanoparticles, plant-derived nanoparticles, bacteria-derived nanoparticles, fungi-derived nanoparticles, and virus-derived nanoparticles in immunotherapy. Compared with synthetic nanomaterials, CDNPs are derived from natural organisms, which have good safety and immunomodulatory properties, are environmentally friendly, and have sustainable sources. It is worth noting that some CDNPs may also have targeting properties and can target specific tissues or cells <italic>in vivo</italic>. CDNPs can also be modified using genetic engineering and chemical modification techniques, which give them unique biological functions required for scientific research and clinical trials. Therefore, CDNPs provide new opportunities for the construction of new immunotherapy strategies. </sec><sec> Despite the great potential of CDNPs, their clinical application faces significant challenges, including their heterogeneity and complexity, which complicate their production, purification, and characterization. Although many preparation methods exist, none of these can fully meet the diverse needs of the application, resulting in differences between batches. At the same time, there is an urgent need to transform small-scale laboratory production into industrial production, but ensuring standardized production processes for CDNPs remains an urgent issue. Difficulties include process consistency and repeatability, as well as controlling production costs, and approaches using genetically engineered cells or synthetic biology may be one of the potential strategies. In addition, since the active biomolecules carried by CDNPs may be immunogenic, the purification process needs to be improved to address the risk of contamination and ensure the quality and safety of CDNPs. The underlying mechanisms of CDNPs’ biological interactions <italic>in vivo</italic> remain to be fully elucidated, including their secretory properties, transport, and interaction with target cells. Therefore, the stability of the nanoparticles <italic>in vivo</italic> and their tissue distribution need to be evaluated, including the degradation rate and release mechanism of the nanoparticles, while optimizing the surface chemistry of the nanoparticles to reduce adverse immune reactions. </sec><sec> In summary, the future of CDNPs in immunotherapy is full of opportunities and challenges. With a deeper understanding of their biological properties and continuous advancement of engineering technology, CDNPs are expected to have a wider range of applications in immunotherapy. Interdisciplinary collaborations integrating achievements in bioengineering, nanotechnology, and immunology are expected to produce innovative, effective, and safe immunotherapy strategies, bringing new hope to patients. </sec>