Chemical Science, Journal Year: 2024, Volume and Issue: unknown
Published: Dec. 23, 2024
We developed a uracil base lesion-gated dumbbell DNA nanodevice (UBLE) that allows on-demand activation and termination of the cGAS-STING pathway in tumor cells, affording precise reliable avenue to enhance cancer immunotherapy.
Language: Английский
MedComm, Journal Year: 2024, Volume and Issue: 5(4)
Published: March 23, 2024
Abstract Since cyclic guanosine monophosphate‐adenosine monophosphate synthase (cGAS)–stimulator of interferon genes (STING) signaling pathway was discovered in 2013, great progress has been made to elucidate the origin, function, and regulating mechanism cGAS–STING past decade. Meanwhile, triggering transduction mechanisms have continuously illuminated. plays a key role human diseases, particularly DNA‐triggered inflammatory making it potentially effective therapeutic target for inflammation‐related diseases. Here, we aim summarize ancient origin defense mechanism, as well triggers, transduction, cGAS–STING. We will also focus on important roles signal under pathological conditions, such infections, cancers, autoimmune neurological visceral inflammations, review drug development targeting pathway. The main directions potential obstacles research diseases cancers be discussed. These advancements expand our understanding cGAS–STING, provide theoretical basis further exploration open up new strategies promising intervention multiple
Language: Английский
Citations
23
Advanced Science, Journal Year: 2024, Volume and Issue: 11(15)
Published: Jan. 17, 2024
As an essential intracellular immune activation pathway, the cGAS-STING pathway has attracted broad attention in cancer treatment. However, low bioavailability, nonspecificity, and adverse effects of small molecule STING agonists severely limit their therapeutic efficacy vivo application. In this study, a peptide-based agonist is first proposed, KLA screened out to activate by promoting mitochondrial DNA (mtDNA) leakage. To precisely block PD-1/PD-L1 multi-stimuli activatable peptide nanodrug (MAPN) developed for effective delivery PD-L1 antagonist (CVR). With rational design, MAPN achieved site-specific release CVR response multiple endogenous stimuli, simultaneously activating blocking ultimately initiating robust durable T cell anti-tumor immunity with tumor growth inhibition rate 78% extending median survival time B16F10 tumor-bearing mice 40 days. Overall, antimicrobial peptides, which can promote mtDNA leakage through damaging membranes, may be potential alternatives giving new insight design novel agonists. Furthermore, presents universal platform synergy peptides.
Language: Английский
Citations
13
Advanced Materials, Journal Year: 2024, Volume and Issue: 36(47)
Published: Oct. 2, 2024
Abstract Nanotechnology has proven its enormous application value in clinical practice. However, current research on nanomedicines mainly focuses developing nanoparticles as delivery carriers to maximize the bioavailability of therapeutic agents, with little attention exploring their potential directly regulate physiological processes. In this study, inspired by lysosomal swelling caused excessive accumulation undegraded substances, work presents a lysosomal‐targeting aggregated nanoparticle (LTANP) for cancer treatment. By rationally engineering surface composition, properties, and interparticle interactions, LTANP achieves efficient tumor selective targeted aggregation lysosomes cells, leading unrelievable swelling, ultimately inducing membrane permeabilization (LMP) cells. Further analysis shows that aggregation‐mediated LMP can effectively trigger immunogenic cell death (ICD) impairing autophagy‐lysosome pathway, evoking robust antitumor immune responses reversing immunogenicity from “cold” “hot” melanoma model. Additionally, combine clinically approved programmed ligand‐1 (PD‐L1) antibodies further unleash T cell‐mediated immunity, significantly enhancing performance, inhibiting recurrence metastasis. This demonstrates engineered nanostructures combating provides novel insights development advanced nanoparticle‐based
Language: Английский
Citations
4
Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(1), P. 46 - 46
Published: Jan. 1, 2025
The emergence of effective immunotherapies has revolutionized therapies for many types cancer. However, current immunotherapy limited efficacy in certain patient populations and displays therapeutic resistance after a period treatment. To address these challenges, growing number drugs have been investigated clinical preclinical applications. diverse functionality peptides made them attractive as modality, the global market peptide-based therapeutics is witnessing significant growth. Peptides can act immunotherapeutic agents treatment malignant cancers. systematic understanding interactions between different host’s immune system remains unclear. This review describes detail roles regulating function cancer immunotherapy. Initially, we systematically elaborate on relevant mechanisms Subsequently, categorize nanomaterials into following three categories: vaccines, anti-cancer peptides, delivery systems. We carefully analyzed overcoming barriers immunotherapy, including multiple strategies to enhance immunogenicity peptide synergistic effect combination with other agents, assemblies functioning stimulators or vehicles deliver agents. Furthermore, introduce status applications discuss weaknesses future prospects materials Overall, this aims comprehension potential lay groundwork research
Language: Английский
Citations
0
Biomaterials, Journal Year: 2025, Volume and Issue: 318, P. 123170 - 123170
Published: Feb. 5, 2025
Language: Английский
Citations
0
Journal of Controlled Release, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 1, 2025
Language: Английский
Citations
0
Advanced Science, Journal Year: 2025, Volume and Issue: unknown
Published: March 27, 2025
Abstract As cancer continues to rank among the leading causes of death, demand for novel treatments has never been higher. Immunotherapy shows promise, yet many solid tumors such as pancreatic or glioblastoma remain resistant. In these, “cold” tumor microenvironment with low immune cell infiltration and inactive anti‐tumoral cells leads increased resistance these drugs. This driven development several drug candidates, including stimulators interferon genes (STING) agonists reprogram system fight off tumors. Preclinical studies demonstrated that STING can trigger immunity cycle increase type I secretion T activation, which subsequently induces regression. Despite promising preclinical data, biological physical challenges persist in translating success into clinical trials. Nonetheless, combination strategies are emerging, investigating other immunotherapies, presenting encouraging results. review will examine potential assess benefits employing them immunotherapy.
Language: Английский
Citations
0
Seminars in Cancer Biology, Journal Year: 2024, Volume and Issue: 106-107, P. 87 - 102
Published: Aug. 31, 2024
Language: Английский
Citations
3
Advanced Materials, Journal Year: 2024, Volume and Issue: unknown
Published: Dec. 4, 2024
Abstract Triple‐negative breast cancer has an immunologically “cold” microenvironment, which leads to resistance current immunotherapy. The activation of stimulator interferon genes (STING) pathway been thought a promising strategy enhance immunotherapy efficacy. In this study, we adopted comprehensive that integrates innate immune responses with tumor‐targeting photothermal therapy (PTT) simultaneously tackle multiple immune‐suppressive mechanisms in cancer. This semiconducting polymeric nanoagonists (DPTT‐Mn Lipo NPs) mediated PTT can effectively initiate tumor cell apoptosis and induce ICD, thereby reprogramming the immunosuppressive TME activating STING. We confirmed modulation through PTT‐mediated ICD effect transactivation cGAS‐STING cells due released dsDNA via such as macrophages DCs. Indeed, DPTT‐Mn NPs‐mediated promoted M1 polarization tumor‐associated macrophages, augmented T‐cell infiltration, facilitated dendritic (DC) maturation, regulated type I factor secretion, leading efficient suppression. Most importantly, combination NPs‐based checkpoint blockade (anti‐PD‐1) elicit long‐term memory besides eradication. Collectively, nano‐system systemically activate antitumor immunity STING potentially establish against recurrence.
Language: Английский
Citations
2
MedComm, Journal Year: 2024, Volume and Issue: 6(1)
Published: Dec. 20, 2024
Abstract Agonists of the stimulator interferon genes (STING) pathway are increasingly being recognized as a promising new approach in treatment cancer. Although progress clinical trials for STING agonists antitumor applications has been slow, there is still an urgent need developing potent with versatile potential applications. Herein, we developed and identified non‐nucleotide agonist called DW18343. DW18343 showed robust activation across different isoforms. Crystallography analysis revealed that binds more deeply into ligand binding domain (LBD) pocket STING‐H232 compared to other such MSA‐2, SR‐717, or cGAMP, which likely contributes its high potency. triggered downstream p‐TBK1/p‐IRF3 signaling, leading production multiple cytokines. Additionally, displayed broad long‐lasting effects various syngeneic mouse tumor models, whether administered locally systemically. Moreover, induced immune memory combat growth rechallenged tumors. Finally, was shown be activator both innate adaptive immunity tissue, potentially explaining strong vivo. In conclusion, serves novel systemic effect through immunity.
Language: Английский
Citations
1