已传文件：photo/1792460769.png
Immune regulation within the body holds promise for benefiting a wider range of cancer patients. Efficiently activating anti-tumor T cells requires "three-signal" dendritic cells (DCs), which integrate antigen, costimulation, and migration programming simultaneously, but this remains a major challenge. Here, we developed a carrier-free peptide–cyclic dinucleotide (CDN) nano-conjugate (PCN) that can simultaneously trigger immunogenic cell death (ICD) in tumors and activate the stimulator of interferon genes (STING) pathway in DCs. Library screening identified ICD-inducing peptides rich in hydrophobic and cationic residues, which promote self-assembly, cell penetration, and ICD potency. Mechanistic studies showed that these peptides trigger overlapping pyroptosis, necroptosis, and apoptosis, with lysosomal damage and protease release being the main upstream drivers. PCN promotes tumor antigen release and cytosolic CDN delivery, resulting in strong STING activation. This dual function induces early cytokine and chemokine responses and generates "three-signal" migratory DCs rich in cDC1s that migrate from tumors to draining lymph nodes, enhancing antigen-specific CD8+ T cell responses. PCN can activate T cells and promote memory formation. Additionally, PCN broadly reprograms the tumor microenvironment toward an anti-tumor immune state. In preclinical models, PCN led to complete tumor rejection in 70% of B16-F10 or CT26 tumor-bearing mice, and combined with T cell activation and memory formation, it provided lasting protection against tumor re-challenge with α-PD-1.
References:
DOI: 10.1002/adma.74918
We focus on customized functional materials in nanomedicine. Based on your experimental needs, we can tailor biofunctional nanomaterials, controlling structure, particle size, and surface modification, with full characterization testing. The plans can be repeatedly optimized with full technical support, supporting targeted delivery, bioimaging, and nano-therapeutics research projects. Feel free to provide your requirements, and we’ll evaluate a custom solution.
Engineer Zhang: 17715390137 Engineer Chen: 18914047343
