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 insi...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.展开更多
Liposomes,as one of the most successful nanotherapeutics,have a major impact on many biomedical areas.In this study,we performed laser scanning confocal microscope(LSCM)and immunohistochemistry(IHC)assays to investiga...Liposomes,as one of the most successful nanotherapeutics,have a major impact on many biomedical areas.In this study,we performed laser scanning confocal microscope(LSCM)and immunohistochemistry(IHC)assays to investigate the intra-tumor transport and antitumor mechanism of GE11 peptideconjugated active targeting liposomes(GE11-TLs)in SMMC7721 xenograft model.According to classification of individual cell types in high resolution images,biodistribution of macrophages,tumor cells,cells with high epidermal growth factor receptor(EGFR)expres sion and interstitial matrix in tumor microenvironment,in addition,their impacts on intra-tumor penetration of GE11-TLs were estimated.Type I collagen fibers and macrophage flooded in the whole SMMC7721 tumor xenografts.Tumor angiogenesis was of great heterogeneity from the periphery to the center region.However,the receptor-binding site barriers were supposed to be the leading cause of poor penetration of GE11-TLs.We anticipate these images can give a deep reconsideration for rational design of target nanoparticles for overcoming biological barriers to drag delivery.展开更多
基金grants from the Natural Science Foundation of China No.30825045.
文摘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supported by National Science Foundation of China(Grant Nos.30825045 and 81273465).
文摘Liposomes,as one of the most successful nanotherapeutics,have a major impact on many biomedical areas.In this study,we performed laser scanning confocal microscope(LSCM)and immunohistochemistry(IHC)assays to investigate the intra-tumor transport and antitumor mechanism of GE11 peptideconjugated active targeting liposomes(GE11-TLs)in SMMC7721 xenograft model.According to classification of individual cell types in high resolution images,biodistribution of macrophages,tumor cells,cells with high epidermal growth factor receptor(EGFR)expres sion and interstitial matrix in tumor microenvironment,in addition,their impacts on intra-tumor penetration of GE11-TLs were estimated.Type I collagen fibers and macrophage flooded in the whole SMMC7721 tumor xenografts.Tumor angiogenesis was of great heterogeneity from the periphery to the center region.However,the receptor-binding site barriers were supposed to be the leading cause of poor penetration of GE11-TLs.We anticipate these images can give a deep reconsideration for rational design of target nanoparticles for overcoming biological barriers to drag delivery.
