Abstract 4152: Synergistic gold nanostar-mediated photothermal and immunotherapy for cancer metastasis treatment
Liu, Y; Maccarini, P; Palmer, GM; Inman, BA; Vo-Dinh, T
Published in: Cancer Research
Cancer has become a severe thread to human health resulting in more than eight million deaths each year. Cancer metastasis is the main mechanism in more than 90 percent of cancer deaths. However, current therapeutic options including chemotherapy and radiation therapy have limited therapeutic effects to treat cancer metastasis. Therefore, there is an urgent need to develop novel methods for cancer treatment. Our group has developed a unique method to synthesize star-shaped gold nanoparticles, gold nanostars (GNS), without using toxic surfactant, which is very suitable for in vivo applications. The synthesized GNS has tip-enhanced plasmonics and tunable strong in the near-infrared “tissue optical window”, enabling it a superior photon-to-heat nanotransducer. The GNS nanoparticles accumulate preferably into tumor with enhanced permeability and retention (EPR) effect after intravenous administration. We have applied GNS for photothermal therapy with 808 nm laser to specifically ablate tumor. Here we report a new cancer treatment method by combing nanophotothermal therapy and anti-PD-L1 immunotherapy. Immunogenic cell death is often insufficient to trigger effective anti-cancer immunity due to the presence of immunosuppressive factors occurring in the tumor microenvironment such as hypoxia, impaired leukocyte trafficking and inhibitory immune checkpoint signaling. The GNS-mediated photothermal ablation can reduce hypoxia and improve leukocyte trafficking to the tumor. In addition, the administration of anti-PD-L1 antibody reverses another critical immunosuppression factor. Experiment results using a mouse bladder cancer model demonstrated that the combined photothermal and immunotherapy have synergistic effect and can not only eradicate primary tumors with laser treatment but also distant metastasis without laser treatment. Furthermore, delayed rechallenge in the cured mice didn't result in new tumor generation, indicating that our combined therapy induced memorized immune response against cancer. The combined GNS-mediated photothermal therapy and anti-PD-L1 immunotherapy has promise to improve therapeutic effect on not only primary tumor but also cancer metastasis.Citation Format: Yang Liu, Paolo Maccarini, Gregory M. Palmer, Brant A. Inman, Tuan Vo-Dinh. Synergistic gold nanostar-mediated photothermal and immunotherapy for cancer metastasis treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4152.
