## 3 Nanostructured Systems for Cancer Immunotherapy
The encapsulation strategy was proven effective, as it demonstrated stronger in vivo cytotoxicity and prolonged activation of NK cells compared to free drugs. Moreover, the proposed delivery alternative resulted in potent immunostimulatory activity, being a promising candidate for antibody-based cancer immunotherapy. Another highly investigated strategy is to combine photothermal therapy with the nano-delivery of immunotherapeutic agents. In this respect, various materials and bioactive substances have been successfully mixed to create synergistic platforms able to release the therapeutic load under the application of magnetic, focused heat, or light fields [25]. For instance, [PERSON] et al. [84] combined the advantages of photothermal therapy and immune checkpoint blockade by creating immunoassay nanocarriers. The researchers fabricated pegylated polydopamine nanoparticles co-loaded with resiquimod and carbon dots that were proven effective against 4T1 breast tumors, inducing a strong antitumor immune response and inhibiting the growth of untreated distant tumors. A different thermosensitive platform for breast cancer was proposed by [PERSON] et al. [85]. The authors reported on the fabrication of a PEL hydrogel incorporating multifunctional nanoparticles (self-assembled from a photothermal agent (indocyanine green) and TLR-7/8 and TLR-9 agonists (i.e., resiquimod and CPG ODNs, respectively)). The system could release the therapeutic load under NIR irradiation, allowing for a sustained antitumor immune response and preventing postoperative breast cancer recurrence and metastasis. Other recently developed nanocarriers triggered photothermally include a semiconducting polymer nanoadjuvant core coated with a thermally responsive lipid shell, which was demonstrated successful  
Figure 5: Visual representation of the gene delivery process through pDNA and mRNA pathways. The use of exogenous mRNA encoding a target antigen leads to protein translation and peptide presentation through MHC Class I and II molecules, a process that activates immune responses and contributes to tumor elimination. Reprinted from an open-access source [39]. in dealing with lung metastasis [68], hollow polydopamine nanoparticles coated with a bacterial outer membrane vesicle (OMV) and a B16-F10 cancer cell (CC) membrane successfully tested against melanoma [86], magnetic nanoparticles covered with a fused coating made of a murine-derived ID8 ovarian cancer cell membrane with a red blood cell membrane that displayed superior results against ovarian tumors [87], and mitochondria targeting phototherapeutic polymeric nanoparticles able to inhibit tumor metastasis [68]. Differently, [PERSON] et al. [88] have reported on the potential use of nanotechnology in combination with photodynamic immunotherapy. Specifically, the authors employed a combination of a tumor-associated macrophage membrane (TAMM) with photosensizer-conjugated nanoparticles. The proposed strategy managed to switch the activation of macrophages from an immunosuppressive M2-like phenotype to a more inflammatory M1-like state, producing immunogenic cell death, contributing to an enhanced efficiency against metastatic tumors, and offering new prospects toward personalized therapy. Another strategy that has the potential to treat cancer is immune checkpoint inhibition [89]. In particular, immune checkpoint blockade (ICB), especially anti-PD1/PD-L1 and anti-CTLA-4 treatments, has been proven successful in treating solid malignancies. High-mutational-load cancers such as [PERSON]'s lymphoma, melanoma, renal cell carcinoma, non-small lung cancer carcinoma, and urothelial bladder carcinoma respond well to anti-PD1/PD-L1 antibody therapy [90]. However, this immunotherapeutic approach fails to ensure long-term remission in a significant number of patients [89]. Consequently, studies have been conducted to overcome its limitations, with important advances being reported by utilizing different delivery vehicles. For instance, [PERSON] et al.