Tumor-Targeted Conjugated Polymer Promotes Photothermal Immunogenic Cell Death and Release of the TLR-9 Immunostimulant Induced Efficient Cancer Immunotherapy

Emerging and promising tools against cancer are theranostic nanoplatforms that combine imaging and therapy. A major challenge is unsatisfactory antitumor efficiency, which is accompanied by a great risk of tumor relapse. Therefore, a multimodal therapeutic functional strategy is highly desirable that can eradicate tumors, preventing tumor relapses and impeding the metastases. Therefore, a combination of photoimmunotherapy in a single therapeutic nanoplatform for efficient tumor-targeted therapy is an efficient task. Herein, we designed a theranostic conjugated polymer polyaniline (PANi)-based synergistic therapeutic model for photothermal immunotherapy (PIT)composed of the EA-PANi@ICG/CpG-FA nanocomposite (NC). This nanosystem was combined with a phototheranostic agent (ICG) with immunomodulation (CpG). On the one hand, PANi promotes photothermal immunogenic cell death (ICD) upon NIR-light irradiation; dying tumors discharge damage-associated molecular pattern signals such as HMBG1, CRT, and ATP, thereby encouraging DC maturation and activation of cytotoxic T lymphocytes. Furthermore, to improve the immune response, CpG promotes the TLR-9 activation in the tumor microenvironment. Therefore, the combinatorial action of NC with CpG leads to complete inhibition of tumor regression by a strong antitumor immune memory effect. We explore that the synergistic effect of the NC in targeted tumor cells improves excellent antitumor effects that have been achieved by photoimmunotherapeutic tactics of cancer therapy.