Enhanced antitumor efficacy of STING agonist MSA-2 by lipid nanoparticles delivering circular IL-23 mRNA and platinum-modified MSA-2 combination

Tian He; Yating Li; Weiqi Li; Muqing Zhang; Guishuan Wang; Peng Zhou; Guoqi Song; Wenqing Li

doi:10.1016/j.mtbio.2025.101446

Enhanced antitumor efficacy of STING agonist MSA-2 by lipid nanoparticles delivering circular IL-23 mRNA and platinum-modified MSA-2 combination

Mater Today Bio. 2025 Jan 3:30:101446. doi: 10.1016/j.mtbio.2025.101446. eCollection 2025 Feb.

Authors

Tian He¹, Yating Li¹, Weiqi Li¹, Muqing Zhang¹, Guishuan Wang¹, Peng Zhou¹, Guoqi Song², Wenqing Li¹

Affiliations

¹ Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong, Jiangsu, 226000, China.
² Department of Hematology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, Jiangsu, 226000, China.

Abstract

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.

Keywords: Circular IL-23 mRNA; Lipid nanoparticles; MSA-2; Platinum-modified MSA-2 (MSA-2-Pt); STING agonist.