Review Gold nanoparticles-mediated photothermal therapy and immunotherapy Yang Liu 1,2,3 , Bridget M Crawford 1,2 & Tuan Vo-Dinh* ,1,2,3 1 Fitzpatrick Institute for Photonics, Duke University, Durham, NC 27708, USA 2 Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA 3 Department of Chemistry, Duke University, Durham, NC 27708, USA *Author for correspondence: tuan.vodinh@duke.edu Cancer has been a signifcant threat to human health with more than eight million deaths each year in the world. Therefore, there is a signifcant need for novel technologies to effectively treat cancer and ultimately reduce cancer recurrences, treatment costs, number of radical cystectomies and mortality. A promising therapeutic platform for cancer is offered by nanoparticle-mediated therapy. This review high- lights the development and applications of various nanoparticle platforms for photo-induced hyperther- mia and immunotherapy. Taking advantage of gold’s high biocompatibility, gold nanoparticles (GNPs) can be injected intravenously and accumulate preferentially in cancer cells due to the enhanced perme- ability and retention effect. Various gold nanoplatforms including nanospheres, nanoshells, nanorods, nanocages and nanostars have been used for effective photothermal treatment of various cancers. GNPs have also been used in immunotherapies, involving cancer antigen and immune adjuvant delivery as well as combination therapies with photothermal therapy. Among GNPs platforms, gold nanostars (GNS) have great therapeutic potential due to their unique star-shaped geometry that dramatically enhances light absorption and provides high photon-to-heat conversion effciency due to the plasmonic effect. This photothermal process can be exploited to specifcally ablate tumors and, more importantly, to amplify the antitumor immune response following the highly immunogenic thermal death of cancer cells. GNS- mediated photothermal therapy combined with checkpoint immunotherapy has been found to reverse tumor-mediated immunosuppression, thereby leading to the treatment of not only primary tumors but also cancer metastasis, as well as to induce effective long-lasting immunity, in other words, an anticancer ‘vaccine’ effect. First draft submitted: 21 June 2018; Accepted for publication: 12 July 2018; Published online: 21 September 2018 Nanoparticles (NPs) have received increasing interest for cancer therapy due to their unique efficacy and specificity in imaging, diagnostics and therapy. This article provides an overview of the research, development and applications of various NP platforms used for photo-induced hyperthermia (HT) and immunotherapy. HT is a treatment where heat is applied to a tumor or organ [1,2]. While high temperature HT (>55 ◦ C) can induce immediate thermal death (ablation) to targeted tumors, mild fever-range HT (40–43 ◦ C) can be used to improve drug delivery to tumors, improve cancer cell sensitivity to anticancer therapy and trigger potent systemic anticancer immune responses [3–6]. NP-mediated thermal therapy offers the potential to combine the advantages of precise cancer cell ablation [7–9] with many benefits of mild HT in the tumor microenvironment, including radio-sensitization of hypoxic regions [10], enhancement of drug delivery [11,12], activation of thermo-sensitive agents [13] and boosting the immune system [14]. Metallic nanostructures have gained particular interest in nanomedicine research due to their ability to interact with electromagnetic radiation, which stems from their confinement of electrons to produce quantum effects. Noble metal plasmonic nanostructures, like gold and silver NPs, are most commonly used due to their relative inertness and visible and near-infrared (NIR) absorption bands. Gold nanoparticles (GNPs) are popular for their biocompatibility while silver NPs have larger molar extinction coefficients, resulting in more sensitive assays. Plasmonic GNPs have been brought to the forefront of cancer research in recent years because of their facile synthesis and surface modification, tunable size, shape and optical properties and biocompatibility. High quality, high yield and size controllable colloidal gold can be quickly prepared by the well-known citrate reduction method [15–17]. Self-assembled GNPs with dithiol-PEG has been developed and applied for photothermal therapy (PTT) [18]. Immunotherapy (2018) 10(13), 1175–1188 ISSN 1750-743X 1175 10.2217/imt-2018-0029 C 2018 Future Medicine Ltd For reprint orders, please contact: reprints@futuremedicine.com