Identification of Cell Receptors Responsible for Recognition and Binding of Lipid Nanoparticles
Effective delivery of lipid nanoparticles (LNPs) and their organ- or cell-type targeting are paramount for therapeutic success. Achieving this requires a comprehensive understanding of protein corona dynamics and the identification of cell receptors involved in the recognition and uptake of LNPs. We introduce a simple, fast, and <i>in situ</i> strategy by a biosensor-based "Fishing" method to uncover protein corona formation on LNPs and identify key receptors of human blood cells that are responsible for the recognition and binding of human plasma corona on the surface of LNPs. Unexpectedly, we observed a significant presence of immunoglobulins with high abundance, especially anti-PEG antibodies, within the LNP corona. These antibodies, along with complement opsonization, drive colony-stimulating factor 2 receptor β (CSF2RB)-mediated phagocytosis by human myeloid cells. These compositions of the human plasma corona and their interactions with neighboring proteins are critical for the recognition and binding of LNPs by cell receptors and cellular uptake. Our findings highlight the pivotal role of anti-PEG antibodies in the circulation and phagocytosis of LNPs <i>in vivo</i>. This approach offers profound insights into nanomaterial behavior <i>in vivo</i>, paving the way for the enhanced design and efficacy of LNP-based therapies.
Authors
- Shengtao Yu (ORCID: https://orcid.org/0009-0003-6954-599X)
- Didar Baimanov (ORCID: https://orcid.org/0000-0002-5805-3303)
- Jing Wang (ORCID: https://orcid.org/0000-0001-8369-7453)
- Fen Liu (ORCID: https://orcid.org/0000-0003-2618-7056)
- Diana Boraschi (ORCID: https://orcid.org/0000-0002-3953-4056)
- Chunying Chen (ORCID: https://orcid.org/0000-0002-6027-0315)
- Pingping Zheng (ORCID: https://orcid.org/0009-0002-2785-3436)
- Liming Wang (ORCID: https://orcid.org/0000-0003-1382-9195)
- Jian Wang (ORCID: https://orcid.org/0000-0002-1278-256X)
- Yuchen Liu (ORCID: https://orcid.org/0000-0003-4691-4951)
- Yuliang Zhao (ORCID: https://orcid.org/0000-0002-9586-9360)
Institutions
- Academy of Medical Sciences (GB)
- Chinese Academy of Sciences (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Peking University (CN)
- Center for NanoScience (DE)
- Applied Nanotech (United States) (US)
- Institute of High Energy Physics (CN)
- National Engineering Research Center for Nanotechnology (CN)
- National Center for Nanoscience and Technology (CN)
- Shenzhen Institutes of Advanced Technology (CN)
- Beijing Proteome Research Center (CN)
- State Key Laboratory of Natural and Biomimetic Drugs (CN)
Publication Details
- Journal
- Journal of the American Chemical Society
- Published
- 2025-02-24
- DOI
- https://doi.org/10.1021/jacs.4c16987
- Citations
- 14
- Primary Topic
- Lipid Membrane Structure and Behavior
- Type
- article
- Field-Weighted Citation Impact
- 11.28
Funders
- National Natural Science Foundation of China
- China Postdoctoral Science Foundation
- Chinese Academy of Medical Sciences
- Ningbo Municipal Bureau of Science and Technology
- Beijing Municipal Natural Science Foundation
- National Key Research and Development Program of China