STING-Activating Polymers Boost Lymphatic Delivery of mRNA Vaccine to Potentiate Cancer Immunotherapy.

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Tác giả: Shengqi Chen, Xiaoyuan Chen, Lingwen Ding, Xiaolin Han, Yaxin Hu, Benhao Li, Bingyu Li, Jianwei Li, Jianping Liu, Min Luo, Qianqian Ni, Yenhui Ong, Ling Peng, Yongling Wang, Zhaoming Wu, Bowei Yang, Longjiang Zhang, Miao Zhang, Mengyao Zhao, Kongfu Zhu

Ngôn ngữ: eng

Ký hiệu phân loại: 620.192 Polymers

Thông tin xuất bản: Germany : Advanced materials (Deerfield Beach, Fla.) , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 689405

The unprecedented success of mRNA vaccines against COVID-19 has inspired scientists to develop mRNA vaccines for cancer immunotherapy. However, using nucleoside modified mRNA as vaccine, though evading innate immune toxicity, diminishes its therapeutic efficacy for cancers. Here, we report a polyvalent stimulator of interferon genes (STING) activating polymer (termed as PD) to bolster the immunogenicity of mRNA vaccine. PD is made of tertiary amine units and conjugated with a biodegradable alkyl chain. Co-formulation of PDs bearing different number of tertiary amines with lipid materials and mRNA resulted in the lipid-like nanoparticles (PD LNPs) which effectively promoted lymphatic delivery and elicited robust immune activation via the STING signaling pathway. Notably, PD with eighteen tertiary amines (PD18) is predominant in balancing immune activity and tolerability. Subcutaneous administration of PD18 LNPs containing ovalbumin (OVA) mRNA enhanced the frequency of antigen specific CD8
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