2. Academic Validation
  3. Improving lipid nanoparticles delivery efficiency of macrophage cells by using immunomodulatory small molecules

Improving lipid nanoparticles delivery efficiency of macrophage cells by using immunomodulatory small molecules

  • Nanomedicine. 2025 Feb 3:64:102809. doi: 10.1016/j.nano.2025.102809.
Lirong Yi 1,  Ziyan Zhang 1,  Tian He 1,  Yating Li 1,  Weiwei Yao 2,  Gangcai Xie 3,  Wenqing Li 4
Affiliations

Affiliations

  • 1 Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong 226000, China.
  • 2 School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao, China. Electronic address: yaoweiwei@uor.edu.cn.
  • 3 Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong 226000, China. Electronic address: gangcai@ntu.edu.cn.
  • 4 Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong 226000, China. Electronic address: liwenqing505@ntu.edu.cn.
PMID: 39904398 DOI: 10.1016/j.nano.2025.102809
Abstract

Nucleic acid drug delivery remains a key challenge in the development of nucleic acid therapy. How to improve the efficiency of nucleic acid delivery is still an important strategy for Lipofectamine 3000 and LNP development. Here, we screened 248 inhibitors or agonists related to immune modulation and identified three small molecules (BP-1-102, SCH58261, and Bropirimine) that could enhance the transfection efficiency to 2-fold to 5-fold of Lipofectamine 3000 and LNP, all of which are currently approved for clinical use in the treatment of the most common malignant tumors. In addition, we used high-throughput RNA Sequencing technology to analyze the mechanisms and found that they were mainly associated with the receptor-mediated endocytosis pathway. Our findings have yielded novel insights that can contribute to the advancement of nucleic acid drugs, enhancing both their efficacy and precision in targeting Cancer therapy.

Keywords

BP-1-102; Delivery efficiency; Endocytosis pathway; Lipid nanoparticles; SCH58261.

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