Black TiO 2 -based nanoparticles as Toll-like receptor stimulators delivery system for enhanced photothermal-immunotherapy of pancreatic cancer

Abstract Background The tumor-specific immune responses, essential for removing residual lesions and preventing tumor metastases, can be stimulated by tumor-associated antigens (TAAs) released following photothermal therapy (PTT). However, due to the immunosuppressed microenvironment of pancreatic ductal adenocarcinoma (PDAC), the TAAs released by PTT are difficult to induce an effective immune response. In this work, we prepared the mesoporous silica (mSiO2) coated black titanium dioxide (bTiO2) photothermal nanoparticles (NPs) for enhanced photothermal-immunotherapy toward PDAC, in which resiquimod (R848) was loaded and DOTA-Gd was conjugated. The NPs are specified as bTiO2@mSiO2@Gd/R848 and abbreviated to NPs/R848. R848 as a kind of Toll-like receptor 7/8 agonist can induce a strong immune response against tumors. Furthermore, DOTA-Gd serves as a magnetic resonance imaging (MRI) contrast agent to improve the T1-weighted MRI performance of the NPs. Results In vitro results of this study show that NPs/R848 could thermally ablate tumor cells and efficiently trigger dendritic cells (DCs) maturation. The results of in vivo investigations demonstrate that the combined use of photothermal-immunotherapy exhibits a significant inhibitory effect on tumor growth. Besides, it promoted maturation of DCs and enhanced infiltration of CD8+, CD4 + T cells to improve the tumor microenvironment. Conclusions Our study anticipate that by encouraging the maturation of DCs, this strategy will enhance the tumor microenvironment and enable the successful photothermal-immunotherapy of PDAC.