Abstract:The combination of therapeutic nucleic acids and chemotherapeutic drugs has shown great promise for cancer therapy. In this study, asialoglycoprotein receptors (ASGPR) targeting-ligand-based liposomes were tested to determine whether they can co-deliver vimentin siRNA and doxorubicin to hepatocellular carcinoma (HCC) selectively. To achieve this goal, we developed an ASGPR receptor targeted co-delivery system called gal-doxorubicin/vimentin siRNA liposome (Gal-DOX/siRNA-L). The Gal-DOX/siRNA-L was created via … Show more
“…We found significantly higher accumulation of Cy3‐RΔF‐LA/miR NPs in the cytoplasm, indicating their efficient delivery and endosomal escape ability. The enhanced cellular uptake for the targeted NPs than the non‐targeted NPs in HCC cells was in agreement with earlier studies which have described the use of LA as the targeting ligand …”
Section: Discussionsupporting
confidence: 92%
“…The enhanced cellular uptake for the targeted NPs than the nontargeted NPs in HCC cells was in agreement with earlier studies which have described the use of LA as the targeting ligand. (19,39,40) miRNAs have been shown to have profound effect on a wide variety of cellular processes including cell proliferation, migration and apoptosis. (6) Functional efficacy of RDF-LA/miR NPs in Huh7 cells with regard to these biological activities was investigated.…”
RΔF-LA/miR NPs showed significantly enhanced delivery of the miRNA which underscores their potential for further development as a therapeutic approach for HCC. (Hepatology 2018;67:1392-1407).
“…We found significantly higher accumulation of Cy3‐RΔF‐LA/miR NPs in the cytoplasm, indicating their efficient delivery and endosomal escape ability. The enhanced cellular uptake for the targeted NPs than the non‐targeted NPs in HCC cells was in agreement with earlier studies which have described the use of LA as the targeting ligand …”
Section: Discussionsupporting
confidence: 92%
“…The enhanced cellular uptake for the targeted NPs than the nontargeted NPs in HCC cells was in agreement with earlier studies which have described the use of LA as the targeting ligand. (19,39,40) miRNAs have been shown to have profound effect on a wide variety of cellular processes including cell proliferation, migration and apoptosis. (6) Functional efficacy of RDF-LA/miR NPs in Huh7 cells with regard to these biological activities was investigated.…”
RΔF-LA/miR NPs showed significantly enhanced delivery of the miRNA which underscores their potential for further development as a therapeutic approach for HCC. (Hepatology 2018;67:1392-1407).
“…Simple PEGylated liposomes [51], advanced stimuli-responsive liposomes [52,53], and targeting liposomes [54,55] have all been constructed for siRNA/chemotherapeutic co-delivery in cancer. Using a PEGylated liposome to co-deliver, BCL2 siRNA with docetaxel successfully inhibited lung cancer in vitr o and in vivo [51].…”
Section: Liposomes or Lipid-based Nanoparticlesmentioning
confidence: 99%
“…Another study demonstrated the targeted co-delivery of siRNA and chemotherapeutic agent to liver tumors [54]. A liposomal carrier for the co-delivery of vimentin siRNA and doxorubicin was prepared from a mixture of lipids: DMKE (O,O’-dimyristyl-N-lysyl glutamate), cholesterol, galactosylated ceramide, POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine), and PEG2000-DSPE (distearoyl phosphatidyl ethanolamine).…”
Section: Liposomes or Lipid-based Nanoparticlesmentioning
RNAi is emerging as a powerful approach in cancer treatment. siRNA is an important RNAi tool that can be designed to specifically silence the expression of genes involved in drug resistance and chemotherapeutic inactivity. Combining siRNA and other therapeutic agents can overcome the multi-drug resistance phenomenon by simultaneously silencing genes and enhancing chemotherapeutic activity. Moreover, the therapeutic efficiency of anti-cancer drugs can be significantly improved by additive or synergistic effects induced by siRNA and combined therapies. Co-delivery of these diverse anti-cancer agents, however, requires specially designed nanocarriers. This review highlights the recent trends in siRNA/anti-cancer drug co-delivery systems under the major categories of liposomes/lipid, polymeric, and inorganic nanoplatforms. The objective is to discuss the strategies for nanocarrier-based co-delivery systems using siRNA/anti-cancer drug combinations, emphasizing various siRNA targets that help overcome multi-drug resistance and enhance therapeutic efficiency.
“…Due to these characteristics, liposomes have previously been used as carriers of anticarcinogens (18)(19)(20). Galactosylated-liposomes, which specifically bind with the asialoglyco protein receptor (ASGPR) on the surface of liver cells are a type of liver targeting preparation (21). These liposomes may be transferred to liver cells via receptor-mediated endocytosis (RME) (22).…”
Liver-targeted drug delivery improves the efficacy of anti-liver cancer agents and reduces systemic toxicity by limiting the bioavailability of these drugs to within tumors. Liver targeting reagents with galactose residues, which selectively combine to asialoglyco protein receptors, have previously been used to improve liposome-encapsulated drug accumulation within liver cells. They lead to a reduction in liver cancer cell growth and have been used to cure certain hepatic diseases. In the present study, curcumol, which is the primary active component of Chinese traditional medicine Rhizoma zedoariae, was encapsulated in galactosylated-liposomes to enhance its anti-liver cancer efficacy. Galactosylated-liposomes and normal liposomes were labeled with propidium iodide. Galactosylated-liposomes with increasing concentrations of galactosylated-stearate (Gal-s) had a notably increased level of uptake in HepG2 cells (hepatoblastoma) compared with SGC-7901 (gastric cancer) and A549 (non-small cell lung cancer) cells. When the percentage of Gal-s reached 20%, liposome uptake plateaued. In the anti-liver cancer experiment, the anti-liver cancer efficacy of galactosylated-curcumol-liposomes increased significantly more compared with normal curcumol liposomes and free curcumol as indicated by cell survival rate and lactate dehydrogenase release rate. Collectively, these results demonstrate that galactosylated-liposomes are able to enhance the liver-targeting effect and anti-liver cancer efficacy of curcumol.
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