Nanocarrier-delivered microRNA to fight sepsis
Scientific news

Nanocarrier-delivered microRNA to fight sepsis

Sepsis is an overreaction of the body’s immune system to an infection. Cytokines flood the bloodstream in an attempt to fight the infection but also cause blood vessels to become leaky. White blood cells escape from the vessels, causing inflammation and damage to surrounding tissue, ultimately leading to multi-organ failure and death. This overreaction is one of the leading causes of death in intensive care units. Researchers under the leadership of Hongkuan Fan, assistant professor in the Department of Pathology and Laboratory Medicine at the Medical University of South Carolina (MUSC), found that sepsis outcomes in a preclinical model significantly improved when a microRNA (miRNA), specifically miR-126, which is known to protect against sepsis, was delivered via a nanocarrier. Almost 67 percent of mice treated with one of the nanocarrier/miR-126 complexes were still alive at seven days vs. just 25 percent of untreated mice. Their findings were reported in Inflammation.
Previous research by Fan’s group has shown that an miRNA — miR-126 — is protective against sepsis. It is a major component of the fluid-filled sacs produced by endothelial progenitor cells. Fan’s group has also shown that these cells, which regenerate the lining of blood vessels, help protect against the vascular damage caused by sepsis.

Assembly of the miRNA/nanoparticle carrier. (©Medical University of South Carolina, Image courtesy of Dr. Hongkuan Fan)

 One obstacle to the clinical use of miRNAs, however, are RNases, whose job it is to seek out and destroy them. Naturally occurring miRNAs are protected from RNases by a fluid-filled sac that covers them or a protein to which they are attached, but those introduced therapeutically have no such protection. The MUSC researchers showed that a proprietary nanocarrier (DEAC-pGlcNAc; Marine Polymer Technologies [Burlington, MA]) could deliver miR-126 effectively in a mouse model of sepsis, protecting it against damage by RNases. Its small size prevented its elimination by the liver, and its electrical charge was such that it was easily taken up by cells. The researchers were also able to verify that the nanoparticle successfully delivered miR-126 into the cell’s nucleus by tagging it with a fluorescent dye. The mIR-126/nanocarrier complex more than doubled the proportion of mice alive at seven days vs. untreated mice in a preclinical model of sepsis (almost 67 percent vs. 25 percent). The nanoparticle, which has antibacterial properties, improved survival even when not complexed with miR-126, though not to a significant degree.