Encapsulation of Platinum Prodrugs into PC7A Polymeric Nanoparticles Combined with Immune Checkpoint Inhibitors for Therapeutically Enhanced Multimodal Chemotherapy and Immunotherapy by Activation of the STING Pathway. Issue 4 (11th December 2022)

• Record Type: Journal Article
• Authors: Gao, Xiangjie; Lei, Guanxiong; Wang, Bin; Deng, Zhong; Karges, Johannes; Xiao, Haihua; Tan, Donghui
• Is Part Of: Advanced science. Volume 10:Issue 4(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-12-11
• Subjects: immunotherapy -- nanoparticle -- oxaliplatin -- polymer with a cyclic seven‐membered ring (PC7A) -- stimulator of interferon genes (STING); Science -- Periodicals; 505
• DOI: 10.1002/advs.202205241
• Languages: English
• ISSNs: 2198-3844

Abstract

Abstract: Tumor immunotherapy has emerged as one of the most promising therapeutic methods to treat cancer. Despite its clinical application, the immunosuppressive tumor microenvironment compromises the therapeutic efficiency of this technique. To overcome this limitation, many research efforts have been devoted to the development of agents that reprogram the immunosuppressive tumor microenvironment through novel mechanisms. Over the last decade, compounds that intervene through the immunogenic stimulator of interferon genes (STING) pathway have emerged with potential for clinical development. Herein, the encapsulation of chemotherapeutic platinum complexes with a polymer with a cyclic seven‐membered ring (PC7A)‐based polymer into pH‐responsive nanoparticles for multimodal therapeutically enhanced chemotherapy and immunotherapy is presented. This study represents the first nanomaterial with a dual activation mechanism of the STING pathway through DNA fragmentation as well as PC7A binding. The combination of these nanoparticles with immune checkpoint inhibitors demonstrates to nearly fully eradicate a colorectal tumor inside the mouse model by chemotherapy and immunotherapy using the STING pathway. Abstract : Despite recent advancements in the field, the immunosuppressive tumor microenvironment is considered as the primary factor for the reduced therapeutic effect of tumor immunotherapy. To overcome this limitation, herein, the encapsulation of a chemotherapeutic platinum complex with a PC7A‐based polymer into pH‐responsive nanoparticles for multimodal therapeutically enhanced chemotherapy and immunotherapy upon dual activation of the STING pathway is presented.