Nanoscale, Journal Year: 2023, Volume and Issue: 15(44), P. 17658 - 17697
Published: Jan. 1, 2023
Camptothecin (CPT) is a cytotoxic alkaloid that attenuates the replication of cancer cells via blocking DNA topoisomerase 1.
Language: Английский
Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)
Published: Oct. 31, 2024
Language: Английский
Citations
16
Aggregate, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 5, 2025
ABSTRACT To improve the long‐term therapeutic efficacy of colorectal cancer, we propose a synergistic treatment strategy involving dual‐pathway, multistep induction hyperimmunity combined with photothermal‐chemotherapy. implement this strategy, infinite coordination polymer nanoparticles (SN38‐Mn(II)‐EGCG ICP NPs) were prepared by coordinating SN38, EGCG, and Mn 2+ . These then coated polydopamine (PDA) grafted folate‐PEG‐thiol (FA‐PEG‐SH) onto their surfaces, producing tumor‐targeting folate‐modified PDA nanocomposites (ICP@FA‐PDA nanocomposites). exhibit particle size 94.9 ± 1.6 nm high drug loading capacity (83.3% 1.5%), release under acidic conditions while maintaining stability in physiological environments. Furthermore, each component within serves multiple functions. Notably, incorporation components triggers powerful antitumor immune effect establishes enduring memory through dual‐pathway approach, which is produced activation cGAS‐STING pathway immunogenic cell death (ICD) four‐component process. Under low‐dose regimen, approach induces generates ultra‐long immunological memory, marked ninefold increase CD8 + T infiltration, fourfold CD4 lymphocytes, reduction Treg cells, fivefold cells. The remarkable therapy achieved combination SN38 EGCG chemotherapy photothermal therapy. In vivo studies demonstrated that mice treated ICP@FA‐PDA complete eradication cancer 21 days, no recurrence observed 60 days. hold significant promise potential for future clinical translation.
Language: Английский
Citations
2
Advanced Materials, Journal Year: 2022, Volume and Issue: 35(8)
Published: Dec. 9, 2022
Tumor metastases and reoccurrences are considered the leading cause of cancer-associated deaths. While highly efficient treatments for eradication primary tumors have been developed, treatment secondary or metastatic remains poorly accessible. Over past years, compounds that intervene through cyclic GMP-AMP synthase-stimulator interferon genes (cGAS-STING) signaling pathway against tumor emerged with potential clinical development. stimulatory DNAs demonstrated activation this pathway, these associated poor bioavailability, stability, cancer selectivity, hindering their use therapeutic applications. Herein, encapsulation a potent chemotherapeutic platinum(II) complex incorporation DNA strands cGAS-STING into multimodal tetrahedral nanostructures (84bp-TDNISD/56MESS ) combined chemotherapy immunotherapy is reported. It found 84bp-TDNISD/56MESS can work as not only drug delivery carrier toxins, but also an immunostimulant agent activate STING antitumor immune responses. In mouse breast model, nanostructure to nearly fully eradicate well secondary/metastatic tumors, hence demonstrating its translational value.
Language: Английский
Citations
58
Advanced Healthcare Materials, Journal Year: 2023, Volume and Issue: 12(19)
Published: March 11, 2023
Abstract As the first line of host defense against pathogenic infections, innate immunity plays a key role in antitumor immunotherapy. The cyclic GMP‐AMP synthase (cGAS)‐stimulator interferon genes (STING) (cGAS‐STING) pathway has attracted much attention because secretion various proinflammatory cytokines and chemokines. Many STING agonists have been identified applied into preclinical or clinical trials for cancer However, fast excretion, low bioavailability, nonspecificity, adverse effects small molecule limit their therapeutic efficacy vivo application. Nanodelivery systems with appropriate size, charge, surface modification are capable addressing these dilemmas. In this review, mechanism cGAS‐STING is discussed agonists, focusing on nanoparticle‐mediated therapy combined cancers, summarized. Finally, future direction challenges nano‐STING expounded, emphasizing pivotal scientific problems technical bottlenecks hoping to provide general guidance its
Language: Английский
Citations
33
Journal of Controlled Release, Journal Year: 2023, Volume and Issue: 362, P. 548 - 564
Published: Sept. 9, 2023
Language: Английский
Citations
33
Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 66(5), P. 3393 - 3410
Published: Feb. 22, 2023
A series of autophagy-targeted antimetastatic clioquinol (CLQ) platinum(IV) conjugates were designed and prepared by incorporating an autophagy activator CLQ into the system. Complex 5 with cisplatin core bearing dual ligands potent antitumor properties was screened out as a candidate. More importantly, it displayed both in vitro vivo expected. Mechanism investigation manifested that complex induced serious DNA damage to increase γ-H2AX P53 expression caused mitochondria-mediated apoptosis through Bcl-2/Bax/caspase3 pathway. Then, promoted prodeath suppressing PI3K/AKT/mTOR signaling activating HIF-1α/Beclin1 The T-cell immunity elevated restraining PD-L1 subsequently increasing CD3+ CD8+ T cells. Ultimately, metastasis tumor cells suppressed synergistic effects damage, promotion, immune activation aroused complexes. Key proteins VEGFA, MMP-9, CD34 tightly associated angiogenesis downregulated.
Language: Английский
Citations
26
Acta Pharmaceutica Sinica B, Journal Year: 2023, Volume and Issue: 14(4), P. 1742 - 1758
Published: Dec. 16, 2023
Mitochondrial membrane remodeling can trigger the release of mitochondrial DNA (mtDNA), leading to activation cellular oxidative stress and immune responses. While role in promoting inflammation hepatocytes is well-established, its effects on tumors have remained unclear. In this study, we designed a novel Pt(IV) complex, OAP2, which composed oxaliplatin (Oxa) acetaminophen (APAP), enhance anti-tumor amplify response. Our findings demonstrate that OAP2 induces nuclear damage, resulting production DNA. Additionally, downregulates expression Sam50, promote mtDNA secretion, double-stranded accumulation ultimately synergistically activating intracellular cGAS-STING pathway. The induced by overcomes limitations Oxa STING pathway simultaneously promotes gasdermin-D-mediated cell pyroptosis. also dendritic maturation enhances quantity efficacy cytotoxic T cells, thereby inhibiting cancer proliferation metastasis. Briefly, our study introduces first small-molecule inhibitor regulates for active immunotherapy research, may provide creative idea targeting organelle therapy.
Language: Английский
Citations
23
Acta Biomaterialia, Journal Year: 2024, Volume and Issue: 176, P. 51 - 76
Published: Jan. 17, 2024
Language: Английский
Citations
11
Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(11)
Published: Jan. 17, 2024
Abstract Activation of stimulator interferon genes (STING) by cyclic dinucleotides (CDNs) has been considered as a powerful immunotherapy strategy. While promising, the clinical translation CDNs is still overwhelmed its limited biostability and resulting systemic immunotoxicity. Being differentiating from current application exogenous to address these challenges, we herein developed one perylene STING agonist PDIC‐NS, which not only promotes production endogenous but also inhibits hydrolysis. More significantly, PDIC‐NS can well reach lung‐selective enrichment, thus mitigates immunotoxicity upon intravenous administration. As result, had realized remarkable in vivo antitumor activity, backward verified on knock out mice. Overall, this study states that function three‐in‐one small‐molecule characterized promoting content possessing good tissue specificity, hence presents an innovative strategy platform for tumor chemo‐immunotherapy.
Language: Английский
Citations
10
Coordination Chemistry Reviews, Journal Year: 2024, Volume and Issue: 508, P. 215796 - 215796
Published: March 17, 2024
Language: Английский
Citations
9