通过脂质纳米颗粒递送环状IL-23 mRNA与铂修饰的MSA-2组合增强STING激动剂MSA-2的抗肿瘤疗效。
Enhanced antitumor efficacy of STING agonist MSA-2 by lipid nanoparticles delivering circular IL-23 mRNA and platinum-modified MSA-2 combination.
作者信息
He Tian, Li Yating, Li Weiqi, Zhang Muqing, Wang Guishuan, Zhou Peng, Song Guoqi, Li Wenqing
机构信息
Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong, Jiangsu, 226000, China.
Department of Hematology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, Jiangsu, 226000, China.
出版信息
Mater Today Bio. 2025 Jan 3;30:101446. doi: 10.1016/j.mtbio.2025.101446. eCollection 2025 Feb.
A next-generation STING agonist MSA-2 is a promising tumor immunotherapy strategy. However, the methods for improving the anti-tumor efficacy of MSA-2 are a lot of effort. We have demonstrated antitumor effect of platinum-modified MSA-2 (MSA-2-Pt) was better than MSA-2. Here, we combined lipid nanoparticles delivering circular IL-23 mRNA (LNP@cIL-23) and MSA-2-Pt strategy, which showed good antitumor efficacy. Firstly, we synthesized a new series of ionizable phospholipids and formulated and optimized an LNP36 for delivering circular IL-23 mRNA. Then, the combination of LNP36@cIL-23 mRNA and MSA-2-Pt induced tumor cell death and immune activation in the tumor with a single i.t. injection. Finally, the combination of LNP36@cIL-23 mRNA and MSA-2-Pt significantly decreased the melanoma B16F10 tumor and prolonged the survival, demonstrating significant anti-tumor effects. This finding provides promising new avenues for STING activation strategies in tumor immunotherapy.
下一代STING激动剂MSA-2是一种很有前景的肿瘤免疫治疗策略。然而，提高MSA-2抗肿瘤疗效的方法需要付出很多努力。我们已经证明铂修饰的MSA-2（MSA-2-Pt）的抗肿瘤效果优于MSA-2。在此，我们将递送环状IL-23 mRNA的脂质纳米颗粒（LNP@cIL-23）与MSA-2-Pt策略相结合，显示出良好的抗肿瘤疗效。首先，我们合成了一系列新的可电离磷脂，并制备和优化了用于递送环状IL-23 mRNA的LNP36。然后，LNP36@cIL-23 mRNA与MSA-2-Pt的组合通过单次瘤内注射诱导肿瘤细胞死亡并激活肿瘤中的免疫反应。最后，LNP36@cIL-23 mRNA与MSA-2-Pt的组合显著减小了黑色素瘤B16F10肿瘤的大小并延长了生存期，显示出显著的抗肿瘤作用。这一发现为肿瘤免疫治疗中STING激活策略提供了有前景的新途径。
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