cGAS-STING, inflammasomes and pyroptosis: an overview of crosstalk mechanism of activation and regulation

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Янв. 9, 2024

Abstract Background Intracellular DNA-sensing pathway cGAS-STING, inflammasomes and pyroptosis act as critical natural immune signaling axes for microbial infection, chronic inflammation, cancer progression organ degeneration, but the mechanism regulation of crosstalk network remain unclear. Main body abstract Cellular stress disrupts mitochondrial homeostasis, facilitates opening permeability transition pore leakage DNA to cell membrane, triggers inflammatory responses by activating cGAS-STING signaling, subsequently induces activation onset pyroptosis. Meanwhile, inflammasome-associated protein caspase-1, Gasdermin D, CARD domain ASC potassium channel are involved in regulating pathway. Importantly, this has a cascade amplification effect that exacerbates immuno-inflammatory response, worsening pathological process autoimmune diseases. Given importance innate immunity, it is emerging new avenue explore mechanisms multiple disease pathogenesis. Therefore, efforts define strategies selectively modulate different settings have been or ongoing. In review, we will describe how mechanistic understanding driving possible therapeutics targeting network, focusing on interacting regulatory proteins, pathways, hub between inflammasomes, Short conclusion This review aims provide insight into roles pyroptosis, highlight some promising directions future research intervention.

Язык: Английский

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Self-Assembled STING-Activating Coordination Nanoparticles for Cancer Immunotherapy and Vaccine Applications

ACS Nano, Год журнала: 2024, Номер 18(15), С. 10439 - 10453

Опубликована: Апрель 3, 2024

The cGAS-STING pathway plays a crucial role in innate immune activation against cancer and infections, STING agonists based on cyclic dinucleotides (CDN) have garnered attention for their potential use immunotherapy vaccines. However, the limited drug-like properties of CDN necessitate an efficient delivery system to system. To address these challenges, we developed immunostimulatory agonists. Here, examined aqueous coordination interactions between metal ions report that mixed with Zn2+ Mn2+ formed distinctive crystal structures. Further pharmaceutical engineering led development functional nanoparticle, termed Zinc–Mn–CDN Particle (ZMCP), produced by simple one-pot synthesis. Local or systemic administration ZMCP exerted robust antitumor efficacy mice. Importantly, recombinant protein antigens from SARS-CoV-2 can be simply loaded during resulting elicited strong cellular humoral responses neutralized SARS-CoV-2, highlighting as self-adjuvant vaccine platform COVID-19 other infectious pathogens. Overall, this work establishes paradigm developing translational nanomedicine drug–metal ion broadens applicability medicine proteins biologics.

Язык: Английский

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Cancer Nanovaccines: Nanomaterials and Clinical Perspectives

Small, Год журнала: 2024, Номер 20(35)

Опубликована: Май 1, 2024

Abstract Cancer nanovaccines represent a promising frontier in cancer immunotherapy, utilizing nanotechnology to augment traditional vaccine efficacy. This review comprehensively examines the current state‐of‐the‐art nanovaccine development, elucidating innovative strategies and technologies employed their design. It explores both preclinical clinical advancements, emphasizing key studies demonstrating potential elicit robust anti‐tumor immune responses. The study encompasses various facets, including integrating biomaterial‐based nanocarriers for antigen delivery, adjuvant selection, impact of nanoscale properties on performance. Detailed insights into complex interplay between tumor microenvironment responses are provided, highlighting challenges opportunities optimizing therapeutic outcomes. Additionally, presents thorough analysis ongoing trials, presenting snapshot landscape. By curating latest scientific findings developments, this aims serve as comprehensive resource researchers clinicians engaged advancing immunotherapy. Integrating design holds immense promise revolutionizing treatment paradigms, provides timely update evolving landscape nanovaccines.

Язык: Английский

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cGAS‐STING pathway agonists are promising vaccine adjuvants

Medicinal Research Reviews, Год журнала: 2024, Номер 44(4), С. 1768 - 1799

Опубликована: Фев. 7, 2024

Adjuvants are of critical value in vaccine development as they act on enhancing immunogenicity antigen and inducing long-lasting immunity. However, there only a few adjuvants that have been approved for clinical use, which highlights the need exploring developing new to meet growing demand vaccination. Recently, emerging evidence demonstrates cGAS-STING pathway orchestrates innate adaptive immunity by generating type I interferon responses. Many agonists developed tested preclinical research treatment cancer or infectious diseases with promising results. As adjuvants, demonstrated their potential activate robust defense various diseases, including COVID-19 infection. This review summarized current developments field special focus latest applications Potential challenges were also discussed hope sparking future interests further adjuvants.

Язык: Английский

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Chitosan-Based Nanomaterial as Immune Adjuvant and Delivery Carrier for Vaccines

Vaccines, Год журнала: 2022, Номер 10(11), С. 1906 - 1906

Опубликована: Ноя. 11, 2022

With the support of modern biotechnology, vaccine technology continues to iterate. The safety and efficacy vaccines are some most important areas development in field. As a natural substance, chitosan is widely used numerous fields—such as immune stimulation, drug delivery, wound healing, antibacterial procedures—due its good biocompatibility, low toxicity, biodegradability, adhesion. Chitosan-based nanoparticles (NPs) have attracted extensive attention with respect adjuvants delivery systems due their excellent properties, which can effectively enhance responses. Here, we list classifications mechanisms action adjuvants. At same time, preparation methods chitosan, NPs, mechanism system introduced. applications NPs protein nucleic acid also This paper reviewed latest research progress chitosan-based adjuvant systems.

Язык: Английский

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Manganese-coordinated mRNA vaccines with enhanced mRNA expression and immunogenicity induce robust immune responses against SARS-CoV-2 variants

Science Advances, Год журнала: 2022, Номер 8(51)

Опубликована: Дек. 23, 2022

It is urgent to develop more effective mRNA vaccines against the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants owing immune escape. Here, we constructed a novel delivery system [IC8/Mn lipid nanoparticles (IC8/Mn LNPs)]with high immunogenicity, via introducing stimulator of interferon genes (STING) agonist [manganese (Mn)] based on newly synthesized ionizable (IC8). was found that Mn can not only promote maturation antigen-presenting cells activating STING pathway but also improve expression by facilitating lysosomal escape for first time. Subsequently, IC8/Mn LNPs loaded with encoding Spike protein SARS-CoV-2 Delta or Omicron variant (IC8/Mn@D IC8/Mn@O) were prepared. Both induced substantial specific immunoglobulin G responses Omicron. IC8/Mn@D displayed strong pseudovirus neutralization ability, T helper 1-biased responses, and good safety. be concluded have great potential developing Mn-coordinated robust immunogenicity

Язык: Английский

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Polymeric nanoparticle-based nanovaccines for cancer immunotherapy

Materials Horizons, Год журнала: 2022, Номер 10(2), С. 361 - 392

Опубликована: Ноя. 29, 2022

Polymeric nanoparticle-based cancer vaccines with the components of antigens ( ex vivo and in situ ) different immune adjuvants.

Язык: Английский

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Adjuvant physiochemistry and advanced nanotechnology for vaccine development

Chemical Society Reviews, Год журнала: 2023, Номер 52(15), С. 5172 - 5254

Опубликована: Янв. 1, 2023

This review provides an introduction of basic principles adjuvanted human vaccines in clinics and summarizes emerging nanotechnology adjuvants vaccine development against cancer infectious diseases.

Язык: Английский

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Overcoming challenges in the delivery of STING agonists for cancer immunotherapy: A comprehensive review of strategies and future perspectives

Materials Today Bio, Год журнала: 2023, Номер 23, С. 100839 - 100839

Опубликована: Окт. 21, 2023

STING (Stimulator of Interferon Genes) agonists have emerged as promising agents in the field cancer immunotherapy, owing to their excellent capacity activate innate immune response and combat tumor-induced immunosuppression. This review provides a comprehensive exploration strategies employed develop effective formulations for agonists, with particular emphasis on versatile nano-delivery systems. The recent advancements delivery systems based lipids, natural/synthetic polymers, proteins are summarized. preparation methodologies nanoprecipitation, self-assembly, hydrogel, along advantages disadvantages, also discussed. Furthermore, challenges opportunities developing next-generation agonist elaborated. aims serve reference researchers designing novel immunotherapy.

Язык: Английский

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Advanced subunit vaccine delivery technologies: From vaccine cascade obstacles to design strategies

Acta Pharmaceutica Sinica B, Год журнала: 2023, Номер 13(8), С. 3321 - 3338

Опубликована: Янв. 10, 2023

Designing and manufacturing safe effective vaccines is a crucial challenge for human health worldwide. Research on adjuvant-based subunit increasingly being explored to meet clinical needs. Nevertheless, the adaptive immune responses of are still unfavorable, which may partially be attributed cascade obstacles unsatisfactory vaccine design. An extended understanding crosstalk between delivery strategies immunological mechanisms could provide scientific insight optimize antigen improve vaccination efficacy. In this review, we summarized advanced technologies from perspective after administration. The engineered with lymph node specific cell targeting ability, cross-presentation, T activation properties, tailorable release patterns achieve protection high precision, efficiency, stability. We hope review can rational design principles inspire exploitation future vaccines.

Язык: Английский

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