Nanomaterial-encapsulated STING agonists for immune modulation in cancer therapy

Abstract

The cGAS-STING signaling pathway has emerged as a critical mediator of innate immune responses, playing a crucial role in improving antitumor immunity through immune effector responses. Targeting the cGAS-STING pathway holds promise for overcoming immunosuppressive tumor microenvironments (TME) and promoting effective tumor elimination. However, systemic administration of current STING agonists faces challenges related to low bioavailability and potential adverse effects, thus limiting their clinical applicability. Recently, nanotechnology-based strategies have been developed to modulate TMEs for robust immunotherapeutic responses. The encapsulation and delivery of STING agonists within nanoparticles (STING-NPs) present an attractive avenue for antitumor immunotherapy. This review explores a range of nanoparticles designed to encapsulate STING agonists, highlighting their benefits, including favorable biocompatibility, improved tumor penetration, and efficient intracellular delivery of STING agonists. The review also summarizes the immunomodulatory impacts of STING-NPs on the TME, including enhanced secretion of pro-inflammatory cytokines and chemokines, dendritic cell activation, cytotoxic T cell priming, macrophage re-education, and vasculature normalization. Furthermore, the review offers insights into co-delivered nanoplatforms involving STING agonists alongside antitumor agents such as chemotherapeutic compounds, immune checkpoint inhibitors, antigen peptides, and other immune adjuvants. These platforms demonstrate remarkable versatility in inducing immunogenic responses within the TME, ultimately amplifying the potential for antitumor immunotherapy.

Putting the sting back in STING therapy: novel delivery vehicles for improved STING activation

“…This results in a low serum half-life and consequently limited efficacy after systemic administration (Lioux et al, 2016). As such, synthetic STING agonists with improved serum stability were developed for clinical application (Chen et al, 2024). Off-target toxicity is still an issue, however, as STING activation in T-cells and B-cells can trigger lymphocyte cell death and apoptosis, facilitating tumor immune evasion and further hindering clinical translation (Wu et al, 2020;Li S. et al, 2022).…”