Targeted delivery of chemically modified anti-miR-221 to hepatocellular carcinoma with negatively charged liposomes

Abstract

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death. Gene therapy was established as a new strategy for treating HCC. To explore the potential delivery system to support the gene therapy of HCC, negatively charged liposomal delivery system was used to deliver miR-221 antisense oligonucleotide (anti-miR-221) to the transferrin (Tf) receptor over expressed HepG2 cells. The liposome exhibited a mean particle size of 122.5 nm, zeta potential of −15.74 mV, anti-miR-221 encapsulation efficiency of 70%, and excellent colloidal stability at 4°C. Anti-miR-221-encapsulated Tf-targeted liposome demonstrated a 15-fold higher delivery efficiency compared to nontargeted liposome in HepG2 cells in vitro. Anti-miR-221 Tf-targeted liposome effectively delivered anti-miR-221 to HepG2 cells, upregulated miR-221 target genes PTEN, P27 kip1 , and TIMP3, and exhibited greater silencing efficiency over nontargeted anti-miR-221 liposome. After intravenous injection into HepG2 tumor-bearing xenografted mice with Cy3-labeled anti-miR-221 Tf-targeted liposome, Cy3-anti-miR-221 was successfully delivered to the tumor site and increased the expressions of PTEN, P27 kip1 , and TIMP3. Our results demonstrate that the Tf-targeted negatively charged liposome could be a potential therapeutic modality in the gene therapy of human HCC.

Dual functionalized liposome-mediated gene delivery across triple co-culture blood brain barrier model and specific in vivo neuronal transfection

“…Conversely, high perfusion rates of organs such as liver, kidneys and heart could disfavor liposome accumulation in these organs. Several studies have explored the efficacy of Tf-liposomes mediated drug/gene delivery and have attributed the low accumulation of liposomes in these organs to rapid blood clearance [49,76–82]. In this study, we observed low liposome fluorescence intensity in liver, kidneys, lungs, heart and spleen and significantly high liposomal accumulation in the brain through NIR imaging and DiR-liposome quantification after 24 h of administration which could be related to the differential blood clearance from these organs.…”

Targeting miRNAs and Other Non-Coding RNAs as a Therapeutic Approach: An Update

“…Similarly, in another study, anti-miR-221 was delivered to the human HCC cell line HepG2 using transferrin-modified NLCs, which demonstrated higher effectiveness in delivering anti-miR-221 to HepG2 cells through the transferrin-mediated endocytosis pathway compared to non-targeted NLCs. These findings demonstrate the potential of using ligand-modified NLCs for the targeted delivery of miRNAs [154].…”

Ligand-modified Nanomaterials for Specific Targeting of Hepatocellular Carcinoma

“…The co-delivery of sorafenib, the first-line medicine for HCC, and DOX by transferrin-conjugated nanoparticles with the albumin shell and polyvinyl alcohol core promoted drug uptake by HepG2 cells, consequently inducing cell death [61] . Besides, transferrin-coated liposomes were used to encapsulate oligonucleotides, such as microRNA-221 inhibitors, to promote HCC cell apoptosis, compared with the nontargeted liposomes [62,63] . Other ligands for TFR targeting have also been widely studied.…”