Amplifying the Antitumor Effect of STING Agonist MSA-2 by Phospholipid Nanoparticles Delivering STING mRNA and Copper-Modified MSA-2 Combination
STING activation is a promising application therapeutic strategy for cancer immunotherapy. In particular, MSA-2 as an oral STING agonist is discovered to have antitumor activity. However, how to improve the antitumor effect of MSA-2 is a very valuable contribution to cancer immunotherapy. Here, we use two strategies to amplify the antitumor effect of MSA-2 by phospholipid nanoparticles delivering STING mRNA and copper-modified MSA-2. We synthesized a new series of ionizable phospholipid nanoparticles and optimized a phospholipid nanoparticle (<b>1A</b>P24) for delivering STING mRNA, increasing the expression of STING protein to bind more MSA-2. Second, we synthesized copper-modified MSA-2 (MSA-2-Cu), which induced cell death by Cu<sup>2+</sup> toxicity. Combining <b>1A</b>P24@STING mRNA and MSA-2-Cu can crucially decrease tumor growth and increase a mouse's survival. It is a new treatment strategy through amplifying the STING pathway.
Authors
- Guoqi Song
- Guishuan Wang
- Tian Tian He (ORCID: https://orcid.org/0009-0004-2580-968X)
- Fei Sun (ORCID: https://orcid.org/0000-0003-3562-1176)
- Yuhang Zhang (ORCID: https://orcid.org/0000-0003-3825-0796)
- Wenqing Li (ORCID: https://orcid.org/0000-0002-2460-7945)
- Mo Wang (ORCID: https://orcid.org/0000-0002-3518-7368)
- Ya Cai
- Peng Zhou (ORCID: https://orcid.org/0009-0004-9567-5488)
Institutions
- Nantong University (CN)
- Affiliated Hospital of Nantong University (CN)
- Institute of Reproductive Medicine (IN)
Publication Details
- Journal
- ACS Applied Materials & Interfaces
- Published
- 2025-04-16
- DOI
- https://doi.org/10.1021/acsami.4c21183
- Citations
- 3
- Primary Topic
- interferon and immune responses
- Type
- article
- Field-Weighted Citation Impact
- 2.39
Funders
- Nantong University
- National Key Research and Development Program of China