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  • Rationally designed anti-autophagy nanosystems for reversing the immunosuppressive network in the tumor environment. Nanomedicine (London, England) Zhang, B. D., Chen, X., Su, J. Y., Zhuo, S. H., Zhao, L., Wu, J. J., Li, W. H., Wang, T. Y., Liu, L., Yang, T., Yang, L. J., Zhao, Y. F., Li, Y. M. 2025; 20 (12): 1429-1440

    Abstract

    To develop a nano-immunotherapy system combining autophagy inhibition and innate immune activation to reverse the immunosuppressive tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC).The pH-responsive polymer PC7A was utilized to co-deliver the autophagy inhibitor chloroquine (CQ) and the STING agonist cyclic diguanylate (CDG), forming the CQCP nanosystem. In vitro and in vivo experiments evaluated autophagy inhibition, MHC-I expression, dendritic cell activation, tumor infiltration of lymphocytes, and survival in PDAC-bearing mice.CQCP enhanced MHC-I expression on PDAC cells by 2.1-fold (p < 0.001) and increased activated dendritic cells (CD86+/CD40+) by 3.5-fold (p < 0.01) in the TME. Tumor-infiltrating CD8+ T cells rose by 42.6% (p < 0.001), and systemic immune activation in peripheral lymphoid tissues was observed. CQCP achieved an 86% survival rate in tumor-bearing mice, significantly outperforming monotherapies or free drug combinations.The CQCP system synergistically reverses PDAC immunosuppression by restoring antigen presentation and activating innate immunity. This dual-targeted strategy demonstrates robust antitumor efficacy and offers a promising immunotherapy approach for PDAC.

    View details for DOI 10.1080/17435889.2025.2508133

    View details for PubMedID 40401367

    View details for PubMedCentralID PMC12143676

  • AlbiCDN: albumin-binding amphiphilic STING agonists augment the immune activity for cancer immunotherapy. RSC medicinal chemistry Zhuo, S. H., Chen, X., Zhao, L., Wang, T. Y., Su, J. Y., Yang, T., Yang, L., Dong, F., Zhao, Y. F., Li, Y. M. 2025; 16 (4): 1797-1807

    Abstract

    The stimulator of interferon genes (STING) has been an attractive target in cancer immunotherapy. However, natural ligand cyclic dinucleotides (CDNs) and CDN derivatives have demonstrated limited efficacy in clinical trials. This limitation stems from the inherent structure of CDNs, which leads to enzymatic degradation, poor cell internalisation, rapid clearance from the tumour microenvironment, and dose-limiting toxicity. In this study, we developed an amphipathic STING agonist, termed albumin-binding CDNs (AlbiCDNs), to enhance the efficacy of c-di-GMP (CDG) via a lipid-conjugated strategy. The lipid provided a platform for albumin hitchhiking, which facilitated the cytoplasmic delivery of CDG without the use of any exogenous components. In addition, incorporating a stimuli-responsive lipid motif further enhanced the cellular release of CDG. Our results indicated that CDG-1C14, an AlbiCDN, efficiently stimulated the maturation and activation of antigen-presenting cells through STING activation. Furthermore, CDG-1C14 exhibited a significant inhibitory effect on the tumour therapeutic model. Therefore, AlbiCDN is a potent platform for cancer immunotherapy that can expedite clinical translation.

    View details for DOI 10.1039/d4md00475b

    View details for PubMedID 40008189

    View details for PubMedCentralID PMC11848399

  • Oligomerization of STING and Chemical Regulatory Strategies. Chembiochem : a European journal of chemical biology Chen, X., Zhuo, S. H., Li, Y. M. 2025; 26 (8): e202400888

    Abstract

    Stimulator of interferon genes (STING) plays a crucial role in innate immunity. Upon the recognition of cytosolic dsDNA, STING undergoes several structural changes, with oligomerization playing a key role in initiating a cascade of immune responses. Therefore, controlling the STING pathway by manipulating STING oligomerization is a practical strategy. This review focuses on the detailed mechanism of STING oligomerization, highlighting its decisive role. It also describes oligomerization-based strategies to regulate STING protein, such as the use of small-molecule agonists and biomacromolecules, highlighting their interaction modes and potential therapeutic applications. This knowledge may lead to the development of innovative approaches for treating cancer and immune disorders.

    View details for DOI 10.1002/cbic.202400888

    View details for PubMedID 39900536

https://orcid.org/0009-0007-3104-1736