Elastin-like polypeptide modified liposomes for enhancing cellular uptake into tumor cells

Polyethylene glycol-modified (PEGylated) liposomes have been widely used because of their long circulation time, but they have a major drawback of limited cellular uptake. In this study, liposomes modified with a thermosensitive biopolymer, elastin-like polypeptide (ELP), were prepared to enhance cellular uptake in tumor cells. Synthesized ELP exhibited an inverse transition temperature (Tt) of 40 °C in serum with hyperthermia treatment and contained a lysine residue for conjugation with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[poly(ethylene-glycol)]-hydroxy succinamide, PEG MW 2000 (DSPE-PEG2000-NHS). ELP was covalently conjugated with liposomes encapsulating a high concentration of doxorubicin (Dox). Size and drug release properties of liposomes were investigated over a range of temperatures. ELP-modified liposomes tended to aggregate but did not show temperature-triggered release by phase transition of ELP molecules. Cellular uptake efficiency of liposomes was evaluated under normothermic and hyperthermic condition. Dox accumulation from liposomes was determined by flow cytometry and confocal microscopy. Higher internalization occurred in the ELP-modified liposomes than in ELP-unmodified liposomes. The results suggest that dehydration of ELP molecules on the liposomal surface can induce efficient cellular uptake, which can improve existing chemotherapeutic efficacy.

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► Thermosensitive elastin-like polypeptide (ELP) was conjugated to the surface of liposomes to overcome the limited cellular uptake occurring with PEGylated liposomes.
► Under hyperthermic conditions, interactions between ELP molecules conjugated to the liposomal surfaces may influence cell-adhesion properties.
► Interactions between ELP molecules decreased the repulsive effect of PEG against cells by reducing the steric hindrance of PEGylated liposomes, and this enhanced the cellular uptake of liposomes.