Multistage Cooperative Nanodrug Combined with PD‐L1 for Enhancing Antitumor Chemoimmunotherapy

Abstract

Combinatorial CpG oligonucleotide (CPG) and chemotherapy drug represent a promising approach to reactivate immune system. However, these two agents possess different physicochemical properties, hindering the application of direct self‐assembly of these two cargos into a single nanostructure. Here, a multistage cooperative nanodrug is developed by the direct self‐assembly of cis‐platinum (CDDP, Pt), l‐arginine (l‐Arg, R), and CPG (defined as PtR/CPG) for antitumor chemoimmunotherapy. First, the CDDP can induce cell apoptosis. Meanwhile, CDDP also promotes the production of H2O2, catalyzing the conversion of l‐Arg into nitric oxide (NO). The generated NO decreases the multidrug resistance of cells toward CDDP. Thus, the synergistic effects of CDDP and NO can trigger immunogenic cell death to produce tumor‐associated antigens (TAAs). The TAAs and CPG will induce the maturation of dendritic cells (DCs) and enhance antigen presentation ability of DCs. In this way, the PtR/CPG can reverse the immunosuppressive microenvironment, sensitizing tumors to immune checkpoint inhibitors mediated by the programmed death‐ligand 1 (PD‐L1) antibody. Furthermore, the PtR/CPG combined with the PD‐L1 antibody decreases the exhaustion and dysfunction of cytotoxic T lymphocytes to elicit durable systemic immune response. As a result, the prepared PtR/CPG nanodrug in combination with PD‐L1 may be highly significant for cancer immunotherapy.

Clinical Prognostic Value of the PLOD Gene Family in Lung Adenocarcinoma

“…Immune regulatory cells inhibit the antitumor response; they recognize and eliminate tumor cells that have undergone mutations, thereby inhibiting tumor growth. In addition, the immune system–mediated inflammatory response can promote tumor growth ( Wang H. et al, 2021 ; Hoteit et al, 2021 ). The alteration of T cell and NK cell compartments found in stage I LUAD lesions suggests that the differential distribution of immune cells is important in the development of immunotherapy strategies for lung cancer ( Lavin et al, 2017 ).…”

PLGA-based drug delivery system for combined therapy of cancer: research progress

“…T cells play a key role in activating the body's immune response in immunotherapy and combination therapy [115]. At the tumor site, T cells are subject to signal regulation from tumor cells or aggregation of immunosuppressive cells, leading to failure or exhaustion of T cells to recognize abnormal cells [133]. Generally speaking, molecules delivered by PLGA micro/nanoparticle [such as antibodies, antigens, immune adjuvants) can directly recruit T cells to the tumor site or block related protein molecules on the surface of tumor cells or increase the exposure of tumor-related antigens to activate T cells.…”

Fluorescent COFs with a Highly Conjugated Structure for Combined Starvation and Gas Therapy

“…l -Arginine ( l -Arg), as an endogenous NO donor with good biocompatibility, is not only very beneficial to the cardiovascular system but also has the ability to achieve precise delivery compared with exogenous NO donors. It also avoids side effects caused by external stimulation (e.g., allergy caused by light stimulation). , However, the pharmacokinetic characteristics of l -Arg after intravenous injection are not very ideal, which will cause huge changes in plasma concentration. , Thus, an effective nanoplatform that can simultaneously deliver sufficient GOx and l -Arg into cancer cells is the key factor determining the final therapy effect.…”

“…It also avoids side effects caused by external stimulation (e.g., allergy caused by light stimulation). 16,17 However, the pharmacokinetic characteristics of L-Arg after intravenous injection are not very ideal, which will cause huge changes in plasma concentration. 18,19 Thus, an effective nanoplatform that can simultaneously deliver sufficient GOx and L-Arg into cancer cells is the key factor determining the final therapy effect.…”