Sepsis
is caused by the invasion of pathogenic microorganisms,
which can lead to excessive expression of toll-like receptors (TLRs)
in cells and uncontrollable amplification of the inflammatory response.
TLR2, as an essential part of the TLR family, has a significant feature
in the identification of innate immune responses. Therefore, blocking
the expression and activation of TLR2 can inhibit the synthesis and
release of inflammatory factors and avoid the occurrence of excessive
inflammatory reactions. Small interfering RNA (siRNA) can selectively
target the silencing or downregulation of pathogenic genes and has
the advantages of high specificity, a strong effect, and fewer adverse
reactions. However, the application of siRNA is limited by its high
molecular weight, poor biostability, and difficulty in passive uptake
into cells. Tetrahedral-framework nucleic acid (tFNA) is a new kind
of three-dimensional nucleic acid nanomaterial, which has the advantages
of good biocompatibility, stable structure, and editability. In this
study, we used tFNA as carriers to deliver siRNA-targeting downregulation
of TLR2 expression for anti-inflammatory therapy. We show that siRNA
can specifically reduce lipopolysaccharide (LPS)-induced TLR2 elevation
and reduce release of inflammatory factors in LPS-induced experimental
sepsis, which provides a new idea for the prevention and treatment
of sepsis.