SYMPHONY: a new concept of plasmonics-amplified immunotherapy for cancer treatment (Conference Presentation)

Cancer is the most common cause of death in people aged less than 85 years and it is estimated that in 2012 there were more than 14.1 million new cancer cases worldwide and 8.2 million deaths that resulted [1]. Nanomedicine has contributed to important advances in health care over the past few decades. In particular, the use of nanoparticles in medicine has attracted increased attention for their unique efficacy and specificity in therapy. A special type of metallic nanoparticles, called “plasmonic” nanoparticles, has received great interest because they exhibit enhanced optical and electromagnetic properties. Plasmonic nanoparticles have unique properties that allow them to amplify the optical properties of the excitation light and thus increase the effectiveness of light-based photothermal tumor ablation. Among nanoparticles used for light-induced photothermal therapy, gold nanostars (GNS) are of particular interest because their structure has multiple sharp branches that produce the numerous curvatures responsible for the ‘lightning rod’ effect that strongly enhances the local electromagnetic field when subject to light stimulation. As with other nanoparticles, GNS sizes can be controlled so that they passively accumulate in tumors due to the enhanced permeability and retention (EPR) effect of tumor vasculature. The combination of the EPR effect and the capacity for efficient photon to heat conversion, make GNS an ideal photothermal transducer for selective cancer therapy at the nanoscale level, as we have demonstrated both in vitro and in vivo. The unique properties of GNS which contribute to plasmonics-amplified immune nanotherapy for cancer, include: (1) plasmonic nano-enhancers of light, (2) nano-targeting of tumor cells, (3) nano-sources for heating tumor cells from the inside (4) nano-activators of the immune system, and (5) synergistic amplification of immunomodulation. These elements will be discussed in detail. We demonstrated that the use of plasmonic nanoparticles in combination with immunotherapy—a treatment we referred to as Synergistic Immuno Photothermal Nanotherapy (SYMPHONY)—can dramatically enhance the efficacy of immunotherapy [2]. Remarkably, we have found that SYMPHONY not only eradicates primary “treated” tumors but also has resulted in the immune-mediated destruciton of distant “untreated” metastatic tumors. This abscopal effect occurred uniquely when nanoparticle tumor heating was used in combination with immunotherapy. This strategy could lead to an entirely new treatment paradigm that challenges traditional surgical resection approaches for many cancers and metastases. Of great importance is the possibility that such an approach can induce long-term immunological memory that can provide protection against tumor recurrence long after treatment of the initial tumors similar to an “anti-cancer vaccine”. [1] World Health Organization, Latest world cancer statistics: Global cancer burden rises to 14.1 million new cases in 2012: Marked increase in breast cancers must be addressed [2] Liu Y, Maccarini P, Palmer GM, Etienne W, Zhao Y, Lee C, Ma X, Inman BA, Vo-Dinh T. Synergistic Immuno Photothermal Nanotherapy (SYMPHONY) for the Treatment of Unresec-table and Metastatic Cancers. Scientific Reports. 7, 8606 (2017).