摘要
Fluorescence labeled small interfering RNAs(siRNAs)were loaded into lipopolyplexes modified with ApoA1(named as rHDL)and administered by intravenous injection.The biodistribution with time of these lipopolyplexes inside the liver and among various cell types was followed using tissue sections by Confocal fluorescence microscopy.At about 0.5 h after tail vein injection at a dose of 0.408 mg/kg,very few fluorescence signals were found in the liver.But then the signals could be seen to accumulate inside hepatocytes as discrete spots and diffused signals at around 2e4 h after injection.Such a distribution and uptake pattern was significantly different from what were observed using the commercial agent Invivofectamine2.0 or DOTAP lipoplexes as the carriers.The differences indicated different mechanisms concerning the in vivo behavior of these carriers.The rHDL carrier system we developed was able to deliver siRNA specifically into hepatocytes while avoiding the uptake by REM cells especially the Kupffer cells.With it’s low toxicity and off target effect,it may be suitable to be developed as a hepatocyte targeting delivery system for siRNA.
基金
grants from the Natural Science Foundation of China No.30825045.
