Journal
NANO LETTERS
Volume -, Issue -, Pages -Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.2c03234
Keywords
lipid nanoparticles; mRNA delivery; secondary lymphoid organs; cell-targeting delivery
Categories
Funding
- National Science Foundation [DMR 2002940]
- NIH [R35 GM141908, S10OD025049]
Ask authors/readers for more resources
An efficient SLOs-targeting carrier was developed in this study by incorporating phosphatidylserine (PS) into the LNP formulation, resulting in enhanced cellular uptake and SLOs-targeted mRNA delivery through monocyte/macrophage-mediated mechanism.
Secondary lymphoid organs (SLOs) are an important target for mRNA delivery in various applications. While the current delivery method relies on the drainage of nanoparticles to lymph nodes by intramuscular (IM) or subcutaneous (SC) injections, an efficient mRNA delivery carrier for SLOs-targeting delivery by systemic administration (IV) is highly desirable but yet to be available. In this study, we developed an efficient SLOs-targeting carrier using phosphatidylserine (PS), a well-known signaling molecule that promotes the endocytic activity of phagocytes and cellular entry of enveloped viruses. We adopted these biomimetic strategies and added PS into the standard four-component MC3based LNP formulation (PS-LNP) to facilitate the cellular uptake of immune cells beyond the charge-driven targeting principle commonly used today. As a result, PS-LNP performed efficient protein expression in both lymph nodes and the spleen after IV administration. In vitro and in vivo characterizations on PS-LNP demonstrated a monocyte/macrophage-mediated SLOs-targeting delivery mechanism.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available