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

IF 27.4 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Advanced Materials Pub Date : 2024-12-23 DOI:10.1002/adma.202412654

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

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Abstract

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+ T cell with immune memory, leading to potent anticancer efficacy that surpassed 2′3’‐cGAMP in both prophylactic and therapeutic cancer models. Additionally, PD18 LNP‐based mRNA vaccine showed conferred resistance to cancer challenge for up to 60 days. Overall, this study offers a new perspective of using STING‐ activating polymer for imparting synergistic activity in mRNA vaccine‐based cancer immunotherapy.

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来源期刊

Advanced Materials 工程技术-材料科学：综合

CiteScore

43.00

自引率

4.10%

发文量

2182

审稿时长

2 months

期刊介绍： Advanced Materials, one of the world's most prestigious journals and the foundation of the Advanced portfolio, is the home of choice for best-in-class materials science for more than 30 years. Following this fast-growing and interdisciplinary field, we are considering and publishing the most important discoveries on any and all materials from materials scientists, chemists, physicists, engineers as well as health and life scientists and bringing you the latest results and trends in modern materials-related research every week.