Targeting of stabilized plasmid lipid particles to hepatocytesin vivoby means of coupled lactoferrin

Abstract

For non-viral gene delivery we prepared stabilized plasmid lipid particles (SPLPs), to which lactoferrin (LF) was coupled as a hepatocyte specific targeting ligand. LF-SPLPs and untargeted SPLPs labeled with [3H]cholesteryloleyl-ether were injected into rats. About 87% of the LF-SPLPs were eliminated from the blood within 5 min, while 80% of untargeted SPLPs were still circulating after 2 h. Fifty-two percent of the LF-SPLPs were taken up by hepatocytes, while non-parenchymal liver cells accounted for 16% of the uptake. Despite the efficient targeting of LF-SPLPs to hepatocytes and their capacity to transfect HepG2 and COS-7 cells in vitro, expression of a reporter gene was not detected in vivo. Overall, covalent coupling of LF to SPLPs leads to massive delivery in hepatocytes after systemic administration. However, these LF-SPLPs are not able to transfect these cells in vivo.

Lactoferrin-modified PEGylated liposomes loaded with doxorubicin for targeting delivery to hepatocellular carcinoma

“…11,13,14 Recent researches demonstrated that Lf might be a potential HCC ligand because of its specific binding with ASGPR. 14,[19][20][21] And Lf exhibits its active targeting ability for HCC cells by the ASGPR endocytosis process. 14,[19][20][21] Our previous work also confirmed the HCC-targeting effect of PLS modified with Lf.…”

“…14,[19][20][21] And Lf exhibits its active targeting ability for HCC cells by the ASGPR endocytosis process. 14,[19][20][21] Our previous work also confirmed the HCC-targeting effect of PLS modified with Lf. 21 Thus, Lf was applied to be the ASGPR-targeting ligand in this work.…”

“…With its specific binding, Lf has been applied to gene delivery successfully, and its ability to target hepatic tumor cells also has been confirmed. [18][19][20][21] In our previous work, an Lf-modified PEGylated liposome (Lf-PLS) system was successfully constructed, and the results demonstrated that Lf-PLS might have great potential for HCC targeting, with low toxicity. 21 However, the feasibility of whether this targeting delivery carrier loaded with chemotherapeutic agent could obtain an enhanced drug accumulation into HCC cells and achieve an increased antitumor effect still needs to be confirmed.…”

Delivery of nucleic acids with a stearylated (RxR)4 peptide using a non-covalent co-incubation strategy

“…Transferrin (Ogris and Wagner, 2002;Russ et al, 2010) Lactoferrin (Huang et al, 2009a;Huang et al, 2009b;Huang et al, 2009c;Weeke-Klimp et al, 2007) Peptide Integrin binding peptide RGD* (Chen et al, 2010;Li et al, 2010;Pike and Ghandehari, 2009) SV40 virus NLS # (Branden et al, 1999;Miller and Dean, 2009) Carbohydrate Galactose (Kasuya and Kuroda, 2009;Letrou-Bonneval et al, 2008;Mukthavaram et al, 2009) Asialofetuin (Arangoa et al, 2003;Diez et al, 2009) Nucleic acid Aptamer (Dhar et al, 2008;McNamara et al, 2006;Zhou et al, 2008) m 3 G-Cap NLS # (Moreno et al, 2009) Lipid…”

Amphiphilic perfluoroalkyl carbohydrates as new tools for liver imaging

“…Less than 10 nm diameter is reported to be appropriate and indeed a modified protein bearing a lactosylated ligand was shown to fully distribute to the liver (Scherman et al, 2008). However, bigger size particles have been reported to reach hepatocytes when decorated with asialoglycoprotein receptor ligand (Weeke-Klimp et al, 2007;Kim et al, 2006). A morphological study of the intersinusoidal space by scanning electronic microscopy showed that this zone exhibit extensive ramifications and was described as a labyrinth of intercellular channels (Motta and Porter, 1974) which could explain the passage of different type of particles.…”