Category Ranking

98%

Total Visits

921

Avg Visit Duration

2 minutes

Citations

20

Article Abstract

Despite potent preclinical antitumor activity, activation of stimulator of interferon genes (STING) has shown modest therapeutic effects in clinical studies. Many STING agonists, including 2',3'-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), show poor pharmacokinetic properties for sustaining STING activation in tumors and achieving optimal antitumor efficacy. Improved delivery of STING agonists and their effective combination with other treatments are needed to enhance their therapeutic effects. Herein, a 2D nanoplatform, cGAMP/MOL, is reported via conjugating cGAMP to a nanoscale metal-organic layer (MOL) for simultaneous STING activation and radiosensitization. The MOL not only exhibits strong radiosensitization effects for enhanced cancer killing and induction of immunogenic cell death, but also retains cGAMP in tumors for sustained STING activation. Compared to free cGAMP, cGAMP/MOL elicits stronger STING activation and regresses local tumors upon X-ray irradiation. Further combination with an immune checkpoint inhibitor bridges innate and adaptive immune systems by activating the tumor microenvironment to elicit systemic antitumor responses.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9529854PMC
http://dx.doi.org/10.1002/adma.202110588DOI Listing

Publication Analysis

Top Keywords

sting activation
16
sting agonists
12
sting
8
therapeutic effects
8
activation
5
nanoradiosensitizer enhances
4
enhances radiotherapy
4
radiotherapy delivers
4
delivers sting
4
agonists potentiate
4

Similar Publications

Type I interferon (IFN-I) is highly prevalent in autoimmune disorders and is intricately involved in disease pathogenesis, including Sjögren's disease (SjD), also known as Sjögren's syndrome. Although the T follicular helper (Tfh) cell response has been shown to drive SjD development in a mouse model of experimental Sjögren's syndrome (ESS), the connection between IFN-I and the Tfh cell response remains unclear. As the activation of stimulator of interferon genes (STING) induces IFN-I production, we first demonstrated that mice deficient in STING or IFN-I signaling presented diminished Tfh cells and were completely resistant to ESS development.

View Article and Find Full Text PDF

The STING pathway has emerged as a therapeutic target in tumor immunotherapy due to its ability to induce interferon responses, enhance antigen presentation and activate T cells. Despite its therapeutic potential, STING pathway-based tumor immunotherapy has been limited by challenges in poor cellular delivery, rapid degradation of STING agonists, and potential systemic toxicity. Recently, advancements in nanotechnology have tried to overcome these limitations by providing platforms for more accurate and efficient targeted delivery of agonists, more moderate sustained STING pathway activation, and more efficient immune presentation and anti-tumor immune response.

View Article and Find Full Text PDF

Acute lung injury (ALI) represents a critical clinical challenge characterized by uncontrolled pulmonary inflammation and disrupted tissue homeostasis, often leading to severe respiratory dysfunction. Current pharmacological interventions and vaccines have demonstrated suboptimal clinical outcomes in modulating disease progression, highlighting the urgent need for innovative therapeutic strategies. A key pathophysiological feature of ALI involves dysregulation of redox homeostasis and excessive pulmonary inflammation.

View Article and Find Full Text PDF

Upon DNA virus infection, cGAS senses viral DNA and triggers MITA (also called STING)-dependent induction of type I interferons (IFN-Is) and other cytokines/chemokines. IFN-Is further activate STAT1/2 to induce interferon-stimulated genes (ISGs) and the innate antiviral response. How the innate antiviral response is silenced in uninfected cells and efficiently mounts upon viral infection is not fully understood.

View Article and Find Full Text PDF

The immune system uses a variety of DNA sensors, including endo-lysosomal Toll-like receptors 9 (TLR9) and cytosolic DNA sensor cyclic GMP-AMP (cGAMP) synthase (cGAS). These sensors activate immune responses by inducing the production of a variety of cytokines, including type I interferons (IFN). Activation of cGAS requires DNA-cGAS interaction.

View Article and Find Full Text PDF