Effects of PEG-Linker Chain Length of Folate-Linked Liposomal Formulations on Targeting Ability and Antitumor Activity of Encapsulated Drug

Abstract

Introduction Ligand-conjugated liposomes are promising for the treatment of specific receptor-overexpressing cancers. However, previous studies have shown inconsistent results because of the varying properties of the ligand, presence of a polyethylene glycol (PEG) coating on the liposome, length of the linker, and density of the ligand. Methods Here, we prepared PEGylated liposomes using PEG-linkers of various lengths conjugated with folate and evaluated the effect of the PEG-linker length on the nanoparticle distribution and pharmacological efficacy of the encapsulated drug both in vitro and in vivo. Results When folate was conjugated to the liposome surface, the cellular uptake efficiency in folate receptor overexpressed KB cells dramatically increased compared to that of the normal liposome. However, when comparing the effect of the PEG-linker length in vitro, no significant difference between the formulations was observed. In contrast, the level of tumor accumulation of particles in vivo significantly increased when the length of the PEG-linker was increased. The tumor size was reduced by >40% in the Dox/FL-10K-treated group compared to that in the Dox/FL-2K- or 5K-treated groups. Discussion Our study suggests that as the length of PEG-linker increases, the tumor-targeting ability can be enhanced under in vivo conditions, which can lead to an increase in the antitumor activity of the encapsulated drug.

Development and application of novel peptide-formulated nanoparticles for treatment of atopic dermatitis

“…Cells were washed and starved in serum-free DMEM for 1 h. After, cells were treated with various concentrations of peptides for 24 h. The CCK-8 reagent was added to each well and incubated for an additional 4 h. The absorbance was measured at 450 nm using a SpectraMax ABS Plus Microplate reader (Molecular Devices, USA). 40–42…”

“…Micelles were also generated using the thin-film hydration method, with varying ratios of DSPE-PEG2k and cholesterol (w/w ratios of 100 : 0, 75 : 25, and 50 : 50). For the peptide loaded micelles (Pal-RMSP1 DP), different weight ratios of peptide solution were added to a polymer thin film (w/w ratios of 4 : 1, 8 : 1, and 16 : 1) and incubated for 1 h. 48–50…”