*4.2. Immunostimulating Peptides*

Although most examples of immunostimulation were reported with fully functional proteins, the use of peptides is also possible. Along this line, Xie et al. reported the use of hollow mesoporous silica-based nanocarriers to deliver two melanoma-derived antigen peptides: the hydrophobic H2-Kb peptide TRP2180–188 (SVYDFFVWL) and the hydrophilic H2-D<sup>b</sup> peptide HGP10025–33 (KVPRNQWL) [121]. In order to achieve the desired double loading, the authors modified their HMSNs with amino groups at the internal space and the mesopores with carboxylates in order to create two di fferent preferential locations for peptides within the HMSNs. Then, to provide adequate retention and colloidal stability, the system was further coated with a lipid bilayer. Furthermore, on this lipid layer, another therapeutic species was included to increase the overall e ffect: monophosphoryl lipid A (MPLA), a Toll-like receptor 4 (TLR4) agonist. The resulting hollow protocells showed time-dependent uptake by murine bone marrow-derived dendritic cells and, according to data shown, induced cell maturation as seen by the overexpression of CD86, TNFα, IFN-γ, IL-12, and IL-4 proteins. When the system was tested against melanoma lung metastasis in murine models, the vaccinated animals showed less tumor growth and creation of metastatic lymph nodes, demonstrating that the system was able to induce an e ffective anticancer response in mice.
