Advanced nanomaterials targeting activation of STING for enhanced cancer immunotherapy

The activation of STING in cancer cells is conducive to inducing apoptosis of cancer cells and activating immune responses for immunotherapy by improving antigen presentation, promoting dendritic cells (DCs) maturity as well as T cells activation, etc. However, the clinical application of STING agonists is still dramatically hindered by various issues, such as poor stability, short half-life, high toxicity, low bioavailability, etc. In recent years, the rapid development in nanotechnology brings new prospects for STING agonists, which promotes the tumor-specific delivery, enhances the efficiency of tumor immunotherapy and reduces systemic toxicity. Based on this, herein, various advanced nanoplatforms as STING agonists for immunotherapy are reviewed. The molecular mechanisms to activate STING pathway are presented at first. Second, the STING activation induced response processes in different cells (including tumor cell, immune cell and other cell) is further described. Then multifarious nanomaterials targeting activation of STING for tumor therapy are highlighted particularly, including metal-based, nucleotide-based and non-nucleotide-based nanoparticles. Finally, the existing problems and challenges about STING agonists are outlined. We hope that this review will provide holistic understanding about nano-sized STING agonists and their application in cancer therapy, paving the way to the translation from bench to bedside in the future.