Solid polymeric microparticles enhance the delivery of siRNA to macrophages in vivo

Therapeutics based on small interfering RNA (siRNA) have a great clinical potential; however, delivery problems have limited their clinical efficacy, and new siRNA delivery vehicles are greatly needed. In this report, we demonstrate that submicron particles (800–900 nm) composed of the polyketal PK3 and chloroquine, termed as the PKCNs, can deliver tumor necrosis factor-α (TNF-α) siRNA in vivo to Kupffer cells efficiently and inhibit gene expression in the liver at concentrations as low as 3.5 μg/kg. The high delivery efficiency of the PKCNs arises from the unique properties of PK3, which can protect siRNA from serum nucleases, stimulate cell uptake and trigger a colloid osmotic disruption of the phagosome and release encapsulated siRNA into the cell cytoplasm. We anticipate numerous applications of the PKCNs for siRNA delivery to macrophages, given their high delivery efficiency, and the central role of macrophages in causing diseases such as hepatitis, liver cirrhosis and chronic renal disease

CCC Men

Four CCC men posing in front of a building, fenced lawns, roads, and range of hills. Writing beneath the photo reads: ""Lewiston Gym"". Writing on the photo includes each man's name.SCS-1150

Two CCC Men

Two CCC men standing on the porch of a CCC building. Writing on the photo reads: ""2-Hogjaws"" in red ink.SCS-1150

Moscow, ID CCC Camp

Side view of Camp Moscow with tents. Writing underneath the photo reads: ""CCC - Camp Moscow, Idaho 19-"".SCS-1150

CCC Man and Sign

Photo of Lieutenant William G. Haltzel, Co. Commander and CCC camp sign. The sign reads: ""CCC Company 1503"". There is some writing in red ink at the bottom of the photo.SCS-1150

CCC Men

A group of four CCC men pose for a picture in the Moscow, ID CCC Camp. Writing under the photo reads: ""CCC Camp Moscow, Idaho 1938-1939"". An arrow pointing to the shadow in the bottom right hand corner is labeled: ""Johnny"".SCS-1150

View of Town

A snow covered view of a town.SCS-1150

CCC District Headquarters

Blurry photo of the CCC District Headquarters at the Lewiston State Normal School. Writing under the photo reads: ""Headquarters"".SCS-1150

Four Men and an Airplane

Four men standing in front of an airplane. Some of the men could be CCC enrollees, others could be pilots, or they could be both. Writing under the photo reads: ""Seattle, Washington"".SCS-1150

Album Cover

John Pollauf photographic album cover. The writing on the interior of the cover of the photo album reads: ""John Pollouf CCC Co 1503 S.C. St. Idaho Collection of photographs taken in Moscow, Idaho between the month of Oct 1938 + March 1939 'Property of one John B. Pollauf Jr. 254 Spring Grove Ave. E. Toledo Ohio.'""SCS-1150