FU-coating pH-sensitive liposomes for improving the release of gemcitabine by endosome escape in pancreatic cancer cells

Abstract

A biodegradable drug delivery system with pH-sensitive property holds vast promise for the improvement of gemcitabine (GEM) in pancreatic cancer cells. Here, a cationic pH-sensitive liposome containing GEM with FU coating (pPSL-FU-GEM, DOTAP: CHEMS: Chol: DSPE-mPEG2000) was designed to improve the bioavailability and efficacy of GEM. After entering the acidic environment of cells, pPSL-FU-GEM could release gemcitabine through an endocytic escape mechanism, preventing it from being degraded by enzymes. The negatively charged fucoidan (FU), which was separated and purified by anion exchange column purification, could target to pancreatic cancer cells and shed, resulting in liposomes uptake by cells. Release studies and intracellular trafficking studies showed that pPSL-FU-GEM released more drug than non-pH-sensitive liposomes in vitro. Meanwhile, pPSL-FU-GEM also showed better anti-proliferative activity than free gemcitabine in pancreatic cancer cells. Overall, we demonstrated the potential of FU-coating pH-sensitive liposomes containing gemcitabine and the drug delivery function in pancreatic cancer cells.