Tumor-Targeted Conjugated\nPolymer Promotes Photothermal\nImmunogenic Cell Death and Release of the TLR‑9 Immunostimulant\nInduced Efficient Cancer Immunotherapy

Abstract

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