Targeted delivery of transferrin and TAT co-modified liposomes encapsulating both paclitaxel and doxorubicin for melanoma

Abstract

The purpose of this study was to develop an efficient dual-ligand based liposomal drug delivery system with targeting specificity as well as properties that would kill melanoma cells. Liposomes modified with transferrin (Tf) and cell-penetrating peptide TAT was prepared, which encapsulated two kinds of chemotherapy drugs, paclitaxel and doxorubicin (Tf/TAT-PTX/DOX-LP). The Tf ligands specifically bind to the overexpressed Tf receptors on the surface of melanoma cells, while the TAT ligands functioned as a classical cell penetrating peptide, helping dual-ligand liposomes be internalized by melanoma cells. The effect of dual-targeting system and ''double-drug'' combination therapy were evaluated both in vitro and in vivo. In vitro, cellular uptake, intracellular distribution and tumor spheroids penetration studies demonstrated that the system could not only be selectively and efficiently penetrate melanoma cells. Besides, apoptosis staining assay and cytotoxicity showed effective anti-tumor capability and obvious synergistic effect of combination therapy of PTX and DOX. In vivo imaging and fluorescent images of tumor section further demonstrated that Tf/TAT-PTX/DOX-LP had the highest tumor distribution. The results of these experiments demonstrated that double-drug liposomal drug delivery systems (DDS) had both enhanced targeting efficiency and increased therapeutic efficacy.

pH‐Responsive PEG‐Shedding and Targeting Peptide‐Modified Nanoparticles for Dual‐Delivery of Irinotecan and microRNA to Enhance Tumor‐Specific Therapy

“…A similar finding using other pH‐sensitive carriers has been reported in a previous study . Moreover, when we observed the CLSM images, most DNR (a probe for irinotecan) released from omLip‐RFKH at pH 6.5 appeared in the nucleus at 24 h (Figure C), revealing that these peptide‐modified nanoparticles tended to successfully avoid drug entrapment by lysosomes and confirming an endosomal escape effect in agreement with a former study . The mitochondria‐targeting and nuclear localization of DNR/Lip‐RFKH in HCT116 cells were further verified using CLSM after 30 min, 3 h, and 24 h‐incubation, as shown in Figure C,D.…”

Transferrin‐bearing liposomes entrapping plumbagin for targeted cancer therapy

“…These results confirm the involvement of clathrin‐mediated endocytosis, which is the main mechanism of nanomedicine internalization (Alshehri et al, ) and caveolae‐mediated endocytosis in the internalization of Tf‐bearing liposomes. The decrease of the drug uptake by the cells was similar to the 20% decrease already reported for Tf/TAT‐liposomes containing doxorubicin in B16 cells, following pretreatment with chlorpromazine (20 μg/ml for 2 h) (Yuan et al, ).…”

Effect of ligand density and PEG modification on octreotide-targeted liposome via somatostatin receptor in vitro and in vivo

“…As a result, the distribution and efficiency of drug encapsulated by longcirculating immunoliposome are improved. Moreover, the therapy effect also has been improved due to its specifically discernment function for target tissues (Zalipsky, 1995, Mercadal et al, 1999, Torchilin et al, 2001, Susumu et al, 2007, Bansal et al, 2016, Yuan et al, 2016.…”