Dual-Targeting Multivalent Aptamer-Drug Hybrids for Synergistic Cancer Immunotherapy - PubMed
3 hours ago
- #Cancer Immunotherapy
- #Multitargeting Therapeutics
- #Aptamer-Drug Hybrids
- Circular, dual-targeting multivalent aptamer-drug hybrids (Dualo-mvApDHsD/S) codeliver doxorubicin and STING agonist for synergistic chemo-immunotherapy.
- Dualo-mvApDHsD/S engage c-Met and CD71 for enhanced tumor uptake via heteromultireceptor-mediated endocytosis, improving intracellular delivery and tumor accumulation in vivo.
- The combination induces genotoxic stress and immunogenic cell death via doxorubicin, while activating cGAS-STING signaling with diABZI to amplify type I interferon responses.
- Therapy remodels the immunosuppressive tumor microenvironment, promoting dendritic cell activation, expanding immune cells, and enhancing cytotoxic CD8+ T cell proliferation and function.
- Single-cell RNA and TCR sequencing show increased TCR diversity, reduced T cell exhaustion, and stronger effector differentiation with the combination therapy.
- Dualo-mvApDHsD/S synergize with PD-1 blockade to achieve durable tumor eradication and long-term protection, highlighting potential for multitarget, multipayload precision therapeutics.