Synergistic Glutathione Depletion and STING Activation to Potentiate Dendritic Cell Maturation and Cancer Vaccine Efficacy.
Jianping LiuYe ZhangBowei YangYingbo JiaRui-Tian LiuLingwen DingZheyu ShenXiaoyuan Shawn ChenPublished in: Angewandte Chemie (International ed. in English) (2024)
Dendritic cell (DC) maturation and antigen presentation are key factors for successful vaccine-based cancer immunotherapy. This study developed manganese-based layered double hydroxide (Mn-LDH) nanoparticles as a self-adjuvanted vaccine carrier that not only promoted DC maturation through synergistically depleting endogenous glutathione (GSH) and activating STING signaling pathway, but also facilitated the delivery of model antigen ovalbumin (OVA) into lymph nodes and subsequent antigen presentation in DCs. Significant therapeutic-prophylactic efficacy of the OVA-loaded Mn-LDH (OVA/Mn-LDH) nanovaccine was determined by the tumor growth inhibition in the mice bearing B16-OVA tumor. Our results showed that the OVA/Mn-LDH nanoparticles could be a potent delivery system for cancer vaccine development without the need of adjuvant. Therefore, the combination of GSH exhaustion and STING pathway activation might be an advisable approach for promoting DC maturation and antigen presentation, finally improving cancer vaccine efficacy.
Keyphrases
- dendritic cells
- papillary thyroid
- signaling pathway
- squamous cell
- lymph node
- regulatory t cells
- immune response
- room temperature
- early stage
- drug delivery
- squamous cell carcinoma
- cancer therapy
- case report
- transition metal
- metal organic framework
- adipose tissue
- metabolic syndrome
- epithelial mesenchymal transition
- induced apoptosis
- locally advanced
- walled carbon nanotubes
- oxide nanoparticles