Multifunctional Mesoporous Polydopamine-Based Systematic Delivery of STING Agonist for Enhanced Synergistic Photothermal-Immunotherapy

Abstract

The therapeutic application of STING agonists in various malignancies has been limited by factors such as the inability of systemic administration and the immunosuppressive tumor microenvironment. Herein, this work reports a mesoporous polydopamine-based multifunctional nanoplatform loaded with STING agonist MSA-2 and chelated with Mn2+ for synergistic photothermal and STING activation-based immunotherapy. The nanoplatform effectively delivers MSA-2 to the tumor site and intelligently releases its contents through acid degradation, facilitated by the photothermal effect. Additionally, the thermal ablation of tumor tissue can induce immunogenic cell death, which helps alleviate the immunosuppressive tumor microenvironment, thereby enhancing the efficacy of MSA-2. Furthermore, Mn2+ works as a dual-acting STING sensitizer and MRI contrast agent which not only boosts the immune response but also allows real-time MRI tracking of the nanoplatform. This strategy is proved highly efficacious both in impeding primary/metastatic tumor and in eliciting a robust tumor-specific immune response. Collectively, an effective multifunctional nanoplatform for the systemic delivery of STING agonist which synergized photothermal therapy and STING pathway activation-mediated immunotherapy is highlighted here to provide new ideas and strategies for optimizing combination therapy for cancer treatment.