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Alternatively, nanoparticles can also be explored as a powerful tool toenhance immunogenicity in cancer immunotherapy. By incorporatingantigens and immunostimulatory agents, nanoparticles can activatedendritic cells and other antigen-presenting cells (APCs), enhancing immuneresponse against the tumor. Nanocarriers augmented ability to targetspecific cell types such as dendritic cells awaken interest in engineeringthem to load and deliver antigens to these immune cells, boosting theirability to stimulate the immune system. From this standpoint, researchershave explored the potential of dendritic cell-targeted nanoparticles toimprove the delivery of tumor antigens, enhancing anti-cancer immunity.Such strategy ensures that tumor antigens are efficiently presented to Tcells, leading to a more effective anti-cancer immune response.Aiming to enhance the chemotherapeutics delivery to cancer cells,researchers have taken advantage of immune cells recruitment to TME, touse them as nanoparticles delivery vehicles. In particular, tumor-infiltratingmacrophages are immune cells that naturally migrate to the TME duringcarcinogenesis through paracrine signaling. From this standpoint,macrophages can be engineered or activated to carry therapeutic agentsand deliver them directly to the tumor site, minimizing systemic sideeffects. Specifically, in such an approach, tumor-infiltrating macrophageswere used as carriers of chemotherapy and photothermal therapy, showingpromising results for in vitro cancer treatment. 2.3. Nanodelivery for Gene TherapyOwing to their numerous advantages over traditional approaches,nanotherapies have emerged as an important tool for gene therapy by usingnanocarriers to deliver genetic material more effectively and safely totarget cells. One of the most significant advances in nanotherapies for genetherapy is the development of non-viral nanocarriers (e.g., polymer-basednanoparticles, lipid-based nanoparticles, carbon nanotubes, goldnanoparticles) offering reduced immunogenicity and stability. Advances innanotechnology have enabled the effective and selective delivery of geneticmaterial (i.e., DNA, RNA, gene-editing tools like CRISPR), by protectingthem from degradation. Despite still poorly explored, in a malignantscenario, nanotherapies hold potential application to more effectivelytarget cancer cells aiming to correct genetic mutations, or activate tumorsuppressor genes. Alternatively, nanocarriers can be engineered to delivergenetic material to different TME components such as cancer-associatedfibroblasts or immune cells, influencing the supporting network thatcontributes to tumor growth and resistance.108Potential of 3D tumor models for nanotherapies pre-clinical screeningVitor M. Gaspar1, Jo%u00e3o F. Mano, et al.