Self-assembled immunostimulatory nanosphere combined with PD-L1 to enhanced cancer chemoimmunotherapy

Abstract

Induction of antigen-specific immune response by maturing dendritic cells (DCs) is a promising strategy for anti-tumor immunotherapy. However, the immunosuppressive tumor microenvironment (TME) and the ineffective tumor-associated antigen (TAAs) presentation of DCs have hindered the efficacy of immunotherapy. Herein, we developed an immunostimulatory nanosphere by direct self-assembly of cyanine5 labeled CPG oligodeoxynucleotide and doxorubicin (Cy5-CPG/DOX). The introduction of Cy5 into CPG could increase the interaction of Cy5-CPG and DOX, accelerating the formation of Cy5-CPG/DOX nanosphere. In vivo, DOX can effectively downregulate the level of regulatory T cells to reverse and abrogate immunosuppressive. Meanwhile, DOX induce immunogenic cell death to produce TAAs, which combined with Cy5-CPG promote the maturation of DCs, improving the TAAs presentation ability of DCs. Thus, the Cy5-CPG/DOX could awaken the innate immune system, sensitizing tumors to immune checkpoint inhibitors mediated by the programmed death-ligand 1 (PD-L1) antibody. In this way, the Cy5-CPG/DOX combined with PD-L1 can decrease the exhaustion of cytotoxic T lymphocytes, eliciting a durable systemic anti-tumor immunity to eradicate cancer. Our work establishes a stable approach for constructing immunostimulatory nanodrug, promoting the development of progressive therapeutic systems.