Antigen‐Capturing Dendritic‐Cell–Targeting Nanoparticles for Enhanced Tumor Immunotherapy Based on Photothermal‐Therapy–Induced In Situ Vaccination

Abstract

In situ vaccines have revolutionized immunotherapy as they can stimulate tumor‐specific immune responses, with the cancer being the antigen source. However, the heterogeneity of tumor antigens and insufficient dendritic cells (DCs) activation result in low cancer immunogenicity and hence poor vaccine response. Here, a new in situ vaccine composed of acid‐responsive liposome‐coated polydopamine (PDA) nanoparticles modified with mannose and loaded with resiquimod (R848) is designed to promote the efficacy of immunotherapy. The in situ vaccine can actively target the tumor site based on the decomposition of the liposome, while the PDA nanoparticles promote photothermal therapy and capture the immunogenic cell‐death–induced tumor‐associated antigens based on the adsorption effect of dopamine‐mimetic mussels. The PDA nanoparticles, which are modified with a mannose ligand, target the DCs and release R848 for activated antigen presentation. As a result, the in situ vaccine not only effectively activates the maturation of the DCs but also significantly enhances their effect on cytotoxic T lymphocyte cells. Furthermore, the vaccine effectively inhibits the distant recurrence and metastasis of tumors via long‐term immune memory effects. Therefore, the in situ vaccine provides a potential strategy for improving the efficacy of cancer immunotherapy.

Global trends in tumor microenvironment-related research on tumor vaccine: a review and bibliometric analysis

“…developed an in-situ vaccine formulation comprising polydopamine (PDA) nanoparticles coated with acid-responsive liposomes. The process of liposome catabolism, which specifically targets the tumor site, coupled with the utilization of PDA nanoparticles to facilitate photothermal therapy, synergistically promotes dendritic cell maturation and significantly enhances the impact on cytotoxic T-lymphocytes ( 96 ). Therefore, in-situ vaccines present a promising approach to enhance the effectiveness of cancer immunotherapy.…”

Nanoparticles in tumor microenvironment remodeling and cancer immunotherapy

“…Then, T cells are activated and improve the potential PD-L1 blockade in cancer immunotherapy [ 404 ]. For stimulation of ICD, various kinds of nanoparticles including polymeric nanostructures [ 405 , 406 ], liposome-modified polysopamine structures [ 407 ], cRGD-functionalized TPGS nanoparticles [ 408 ], iron (II)-cytosine-phosphate-guanine nanoparticles [ 297 ] and iron oxide nanostructures [ 409 ] have been introduced to enhance cancer immunotherapy. Therefore, nanoparticle-mediated ICD can cause stimulation of dendritic cells to activate T cells in lymph nodes for increasing cancer immunotherapy.…”

Stimuli-Responsive Polymeric Nanomedicine for Enhanced Cancer Immunotherapy

“…Besides the strategies for PTT combined with immunotherapy, nanoparticles for targeting antigen-capturing DCs, 157 AuNPs-carrying T cells for ACT and PTT 158 have been proposed. Antigen-capturing DC-targeting nanoparticles were synthesized using mannose-modified TLR agonist-loaded PDA, and the modified PDA was coated with liposomes.…”